Housing for holding a flexible bioprocess bag

ABSTRACT

A support housing for a flexible bioprocess bag, the housing comprising at least one side wall having a first segment and a second segment, the first segment movable in relation to the second segment between an open and a closed position, wherein at least a supporting part of the housing is translatable from an operating position to a bag loading position, wherein the supporting part comprises one or more retainers for holding the flexible bioprocess bag upon re-translation of the supporting part to the operating position and movement of the first segment to the closed position, and wherein the first segment comprises a first drive unit for connecting and driving a first mixing unit in the flexible bioprocess bag.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a National Stage of International Application No.PCT/EP2017/084621 filed on Dec. 27, 2017, which claims priority toIndian Patent Application No. 201611044877 filed on Dec. 29, 2016,Indian Patent Application No. 201611044898 filed on Dec. 29, 2016 andIndian Patent Application No. 201741011286 filed on Mar. 30, 2017, allof which are incorporated herein in their entireties.

FIELD OF THE INVENTION

The subject matter disclosed herein relates to housings for holding aflexible bioprocess bag, to flexible bioprocess bags and to methods forloading a flexible bioprocess bag into a support housing. The flexiblebioprocess bag can be a flexible bioprocess bag used for holdingingredients, such as a bioreactor bag.

BACKGROUND OF THE INVENTION

Single-use or disposable systems are rapidly increasing in differentindustries and especially in industries that require use of cleanprocessing equipment and clean rooms, such as in the biopharmaceuticalindustry. Disposable systems are flexible and cost-effective andcleaning processes may be reduced or eliminated. Traditional systemscomprise re-usable wetted parts in fluid contact which are typicallybuilt as stainless steel installations (tubes and vessels), which needto be cleaned or sterilized in between processes or batches.Sterilization is typically done by steam sterilization, which requirestechnical infrastructure and is a complex and time-consuming process. Incontrast, disposable components in disposable systems provide surfacesin fluid contact that are preferably pre-sterilized and pre-qualified toall regulatory requirements. Disposable or single-use systems arereplaced in between processes to eliminate cleaning and sterilizationissues. Due to lower complexity in systems and auxiliary systems,disposable systems are therefore easy to adapt to different productionpurposes and facilities. Further, it is easy and less costly to change aproduct line compared to traditional equipment. Disposable systems mayprovide also improved reliability as well as product and operator safetyin biopharmaceutical processing.

There are several kinds of disposable systems, such as mixing systems,in which disposable containers or bags are used. These containers orbags comprise often sheets of flexible material, such as plastic,plastic laminates or corresponding materials. A flexible bioprocess bagrefers to a bag or pouch made of walls of similar structure preferablyassembled by welding. These walls may be made of a mono or multilayerfilm including or not a barrier layer based on a barrier polymer likeethylene vinyl alcohol polymer (EVOH). Generally, these films may havean inner layer (in contact with the contents of the bag when filled)based on a polyolefin, preferably an ultra-low density polyethylene,pref. medical grade (ULDPE). The bag may be of cylindrical shape.Although cylindrical flexible bioprocess bags are difficult tomanufacture, the cylindrical shape can be approximated and achieved bywelding of multiple film panels of suitable size and shape. However, theflexible bioprocess bags can equally have cubic or parallel piped shape.Various processing and pre-conditioning steps need to be performedwithin these bags such as for example pre-sterilization.

One type of mixing system in which such containers or bags can be usedis a bioreactor system in which cells or microorganisms can grow. Here,the bags are provided as closed and pre-sterilized components in orderto avoid any contamination or inhibition in the growth of themicroorganisms or cells intended for cultivation in the bioreactor.

Mixing systems include also systems used to prepare for example bufferand media, which may involve the dissolving of salts, the homogenizationof suspended solids or similar.

Mixing systems include also systems for performing reactions, treatments(e.g. virus inactivation), and separations (2-phase system formation,extraction, flocculation), among other fluid processing and fluidtreatment operations.

Mixing systems may comprise a support or vessel which supports or housesa disposable bag or container of the above-mentioned type. The supportmay be a support plate or tray for a bioreactor bag of a kind used in GEHealthcare WAVE Bioreactor®. The WAVE bioreactor is an example of amixing system without an active mixing element, such as an agitator orimpeller, submerged in the fluid. With the WAVE system, mixing isobtained by rocking the container and the platform holding thecontainer. The vessel may also be a tank-type support which has asubstantially cylindrical form, for example substantially circularcylindrical and is made of rigid material such as stainless steel toprovide sufficient support for the flexible bioprocess bag or container,for example of a kind used in Xcellerex XDR™ Single-use bioreactors. TheXcellerex bioreactor is an example of a mixing system comprising anactive mixing element, here a rotating impeller. The flexible containeror bag is placed inside the vessel in an accurate manner so that forexample different pipelines or tubes, mixers and sensors can beconnected to the bag properly and accurately. WO 2005/118771 A2discloses a disposable system of this kind.

In general, mixing systems and mixing containers or bags may be designedas a stand-alone system; or, may be part of a bioreactor, a fluidstorage vessel, fluid mixing unit and so on.

Containers may vary in size from about 0.1-2000 litres. Especially atlarger sizes (>20 litres), the use of vessels or rigid supportstructures is preferred and required for reinforcing the containers orto enable the connection of different pipelines or sensors to thecontainers.

The disposable containers or bags often comprise portions of rigid orsemi-rigid materials for connection of tubing, ports, attachment pointsor general reinforcement. These rigid or semi-rigid portions provide aplatform for safe and secure attachment of for example sensors,pipelines for fluids (both gas and liquid) and mixers. Further, therigid or semi-rigid parts can reinforce and stabilize the containers andtherefore facilitate placing of the containers into mixing vessels inaccurate manner.

Bioprocess or mixing bags are typically provided in a housing of thebioreactor. There are numerous ways to load a flexible bioprocess bag inthe housing. A standard solution for loading the flexible bioprocess baginto the rigid housing is to utilize an opening in the bioreactor wallto insert the collapsed bag through this opening (XDR Bioreactor™, GEHealthcare™. A reinforcement plate is then used to support the bagacross the surface of the opening during processing and when filled withliquid. This loading method is applicable to bags that can be collapsedto a small size. Another method of loading a flexible bioprocess bag isto utilize one or multiple door segments in the rigid housing of thebioreactor. By closing the door(s) after bag loading, the rigid housingdoes support the bag during processing and when filled with liquid. Theflexible bioprocess bag may also be loaded through an opening at the topof the rigid housing. However, this method is typically only applicablefor smaller bioreactors with a height of the rigid housing not exceedingapproximately 50 cm.

The above described bag loading methods all have the disadvantage of theoperator needing to access the internal of the bioreactor and the rigidhousing to arrange the bag in its required position, for example bydocking a magnetic impeller in the bag to a magnetic drive plate in thebottom of the rigid housing. This issue with poor usability andergonomics is in proportion to the size of the reactor.

Another loading method that provides better access to the bottom of therigid housing is described in the product Mobius® 2000 Liter Single-UseBioreactor from Millipore™. Here a bottom loading drawer is used. Thedrawer is guided on rails and can be drawn out below the rigid housing.A single-use bioreactor can be provided inside the drawer which then ispushed back to a position below the rest of the rigid housing. Anotherexample can be seen in the ABEC CSR-Bioreactor™. Here a small carriageis provided as a bottom part of the rigid housing. The carriage can bemoved to a loading position outside the rigid housing. The single usebioreactor is provided on the carriage which then is moved back into therigid housing.

A drawback with the movable bottom part of the Millipore device is thatcable and/or tubing carriers have to be employed to accommodate thechange in distances between cable and/or tubing connection points at thebioreactor bottom and the system, respectively. Due to the linear motionand displacement of the movable bottom, these cable carriers are notstatic but need to be movable and flexible, which requires additionalspace underneath the rigid housing and bioreactor. Also, handling thetubing and cables during the operation of the bioreactor device may becumbersome.

Another solution for loading the bag is where a bag is placed on thebottom of a rigid housing. A hoist connected to an end of the bag isused to lift and vertically orient the bag within the rigid housing. Therigid housing may have a door that can be opened to access the bottom ofthe rigid housing. An operator needs to climb up along the side of therigid housing of the bioreactor using a ladder to connect the cableand/or tubes to ports of the bag. The ladder may be an integral part ofthe rigid housing or a separate ladder can be used. This loading methodalso poses usability issues and poor ergonomics for the operator. Inother solutions, the operator may need to manually lift the bag toconnect its end to a stand of the rigid housing. The stand facilitatesthe bag to be oriented vertically within the rigid housing. The operatormay need to use a ladder to climb along the side of the housing forconnecting the bag to the stand and also connect the tubes to bag portsand other cables. The connection or installation of exhaust air filtersat the top of the bioreactor and bag is another operational step duringbag installation and/or processing that requires the operator tointeract with the top of the bag and reactor, and requires the operatorto climb a ladder or enter a gallery at the top of the reactor vessel.

BRIEF DESCRIPTION OF THE INVENTION

The object of the invention is to provide a support housing for aflexible bioprocess bag, where the flexible bioprocess bag can be loadedin the housing in an easy way with good ergonomics for the operator.This is achieved by the housing comprising a side wall and a supportingpart connected to a side wall to tiltably translate with respect to alongitudinal axis of the housing from an operating position to a bagloading position, wherein the supporting part comprises one or moreretainers for holding the flexible bioprocess bag upon re-translation ofthe supporting part to the operating position. In some embodiments, theside wall comprises a first segment and a second segment, the firstsegment movable in relation to the second segment between an open and aclosed position.

This is also achieved by a support housing having an upright side walland a supporting part connected to the upright side wall to tiltablytranslate with respect to a longitudinal axis of the housing from anoperating position to a bag loading position, wherein the supportingpart comprises one or more retainers for holding the flexible bioprocessbag upon re-translation of the supporting part to the operatingposition. In some embodiments, the upright side wall comprises a firstsegment and a second segment, the first segment movable in relation tothe second segment between an open and a closed position.

This is also achieved by a method of providing a flexible bioprocess bagin a bioreactor. The bioreactor comprises a housing having an uprightside wall and a supporting part arranged to tiltably translate withrespect to a longitudinal axis of the housing from an operating positionto a bag loading position. The method comprises loading a flexiblebioprocess bag on the supporting part arranged to the bag loadingposition; securing the flexible bioprocess bag on the supporting partusing one or more retainers; and re-translating the supporting part tothe operating position thereby positioning the flexible bioprocess bagwithin the housing.

The supporting part is tiltably translatable between a verticalorientation and a horizontal orientation. In the horizontal orientation,the flexible bioprocess bag is loaded on the supporting part in aconvenient manner for an operator. The operator can place the flexiblebioprocess bag on top of the supporting part and make requiredconnections to the flexible bioprocess bag. Subsequently, the supportingpart is translated or moved to the vertical orientation making the bagloading process easy. While loading of the flexible bioprocess bag and acorresponding loading position will be discussed hereafter, it isunderstood that the technical and ergonomic advantages of the inventionwith its improved loading position during bag loading equally applyduring the removal of the bag. The supporting part can be retranslatedfrom the vertical orientation to the horizontal orientation and theflexible bioprocess bag can be removed from the supporting part. Theside wall of the support housing is designed with a double jacket toaccommodate heat exchange features and transfer heat to or from theflexible bioprocess bag and bioreactor fluid volume to the jacketedvessel or vice versa. The heat exchange features enable the transfer ofheat from support housing to the flexible bioprocess bag and thebioreactor fluid in the bag.

A method of cultivating cells in a bioreactor is disclosed. Thebioreactor includes a support housing comprising a side wall having afirst segment and a second segment, the first segment movable inrelation to the second segment between an open and a closed position;wherein at least a supporting part of the first segment is arranged tobe translatable from an operating position to form a bag loadingposition. The method includes loading the flexible bioprocess bag on thesupporting part arranged in the bag loading position; securing theflexible bioprocess bag on the supporting part using one or moreretainers; re-translating the supporting part to the operating positionthereby positioning the flexible bioprocess bag within the housing;feeding culture medium and cells into the flexible bioprocess bag; andcultivating the cells in the flexible bioprocess bag.

A flexible bioprocess bag for holding fluids loadable in a supporthousing is disclosed. The flexible bioprocess bag comprises at least oneinterface plate, an interface plate comprising at least one fluidconnection to interior of the flexible bioprocess bag, wherein theflexible bioprocess bag in a folded configuration exposes the interfaceplate such that the interface plate is attachable to an interfaceretainer on a supporting part of the support housing, the flexiblebioprocess bag extends in a dimension along the supporting part whileremaining unfolded narrower than the width of the supporting part; and amating retaining member attachable to a retainer provided at thesupporting part. One advantage with the disclosed is that the bagloading process becomes more convenient because the flexible bioprocessbag can be easily placed on the supporting part in the horizontalorientation. All tube or cable connections to the flexible bioprocessbag and connection to a driving unit of the flexible bioprocess bag canbe done at floor level by the operator which avoids climbing on top ofthe bioreactor.

A flexible bioprocess bag comprising a first mixing unit configured foragitating a content of the flexible bioprocess bag and a second mixingunit, adjacent to a sparging unit, and configured for controlling thesize and distribution of bubbles emanating from the sparging unit, isfurther disclosed.

Further, a support housing for a flexible bioprocess bag is disclosed,comprising a first drive unit and a second drive unit for connecting anddriving a first mixing unit and a second mixing unit in a flexiblebioprocess bag when mounted in said support housing, wherein said firstdrive unit is provided on a side wall or side wall segment of saidsupport housing and wherein said second drive unit is provided on abottom wall or bottom wall segment of said support housing.

A more complete understanding of the present invention, as well asfurther features and advantages thereof, will be obtained by referenceto the following detailed description and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a illustrates a support housing including a side wall and asupporting part in accordance with an embodiment of the invention;

FIG. 1 b illustrates a side view of the support housing illustrated inFIG. 1 a;

FIG. 1 c illustrates the support housing of FIG. 1 a having thesupporting part in an extended position;

FIG. 1 d illustrates a support housing including a side wall having afirst segment and the second segment in accordance with an embodiment ofthe invention;

FIG. 1 e illustrates a support housing including a side wall having afirst segment and the second segment in accordance with an embodiment ofthe invention;

FIG. 1 f illustrates a base segment tiltably movable with respect to thefirst segment according to an exemplary embodiment;

FIG. 1 g illustrates a support housing having a first segment that iscollapsible according to an exemplary embodiment;

FIG. 1 h illustrates a support housing having a first segment comprisinga first portion and a second portion according to an embodiment of theinvention;

FIG. 1 i illustrates a support housing having a first segment comprisinga first portion, a second portion and a third portion according to anembodiment of the invention;

FIG. 1 j illustrates a support housing having a first segment that iscollapsible with a stand for supporting the first segment according toan exemplary embodiment;

FIG. 2 illustrates a flexible bioprocess bag capable of holding fluidand other contents according to an embodiment of the invention;

FIG. 3 illustrates a support housing having a retainer in a supportingpart according to an embodiment of the invention;

FIG. 4 illustrates a flexible bioprocess bag according to an exemplaryembodiment of the invention;

FIG. 5 illustrates an operator loading the flexible bioprocess bag on asupporting part of a support housing according to an embodiment of theinvention;

FIG. 6 illustrates the flexible bioprocess bag of FIG. 5 loaded in thesupport housing according to an embodiment of the invention;

FIG. 7 illustrates a port of the flexible bioprocess bag of FIG. 5according to an embodiment of the invention;

FIG. 8 a illustrates a support housing for holding a flexible bioprocessbag according to an exemplary embodiment;

FIG. 8 b illustrates an opening of the supporting part of the supporthousing according to an embodiment;

FIG. 8 c illustrates an opening of the supporting part of the supporthousing according to an embodiment;

FIG. 9 illustrates a support housing having a receiver for holding a baginterface plate of the flexible bioprocess bag according to anembodiment of the invention;

FIG. 10 illustrates a support housing having tube trenches for receivingand holding tubes connected to the support housing according to anembodiment of the invention;

FIG. 11 illustrates a support housing having a supporting part havingmultiple receivers capable of receiving mixing units of the flexiblebioprocess bag according to an embodiment;

FIG. 12 illustrates a flexible bioprocess bag having multiple mixingunits to be arranged on the supporting part of FIG. 11 ;

FIG. 13 illustrates an exemplary flexible bioprocess bag arranged in asupport housing according to an embodiment;

FIG. 14 illustrates a support housing for holding a flexible bioprocessbag according to an embodiment;

FIG. 15 illustrates a support housing having a first segment (i.e. thesupporting part) that is operably connected to the second segmentaccording to an embodiment;

FIG. 16 illustrates a flow diagram of a method of providing a flexiblebioprocess bag in a support housing according to an embodiment;

FIG. 17 illustrates a method for cultivating cells in a flexiblebioprocess bag arranged in a support housing according to an exemplaryembodiment; and

FIG. 18 illustrates an exemplary flexible bioprocess bag according to anembodiment.

FIG. 19 illustrates computerized fluid dynamics (CFD) simulations ofmixing in a vessel with a), c), e) a bottom-mounted impeller and b), d),f) a side wall-mounted impeller.

FIG. 20 illustrates the flow pattern from the CFD simulation of the sidewall-mounted impeller of FIG. 19 b ), d) and f).

FIG. 21 illustrates a flexible bioprocess bag with first and secondmixing units, mounted in a support housing with first and second driveunits, according to certain embodiments.

FIG. 22 illustrates a flexible bioprocess bag with first and secondmixing units, during mounting in a support housing with first and seconddrive units, according to certain embodiments.

FIG. 23 illustrates a sparging unit with a second mixing unit accordingto certain embodiments.

FIG. 24 illustrates a support housing and a flexible bioprocess bag withmultiple mixing units mounted on a single shaft. a) closed (working)position, b) open (loading) position.

FIG. 25 illustrates a support housing and a flexible bioprocess bag withmultiple mixing units mounted on a single shaft. a) closed (working)position, b) open (loading) position.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings that form a part hereof, and in which is shown byway of illustration specific embodiments that may be practiced. Theseembodiments are described in sufficient detail to enable those skilledin the art to practice the embodiments, and it is to be understood thatother embodiments may be utilized and that logical, mechanical and otherchanges may be made without departing from the scope of the embodiments.The following detailed description is, therefore, not to be taken aslimiting the scope of the invention.

As discussed in detail below, embodiments of a support housing for aflexible bioprocess bag, wherein the flexible bioprocess bag can beloaded in the support housing in an easy way with good ergonomics forthe operator. This is achieved by the support housing comprising a sidewall having a wall portion movable between an open position and a closedposition. A supporting part of the support housing is arranged to betranslatable from an operating position to a form a bag loadingposition. The supporting part may tiltably translate between a verticalorientation and a horizontal orientation. The supporting part comprisesone or more retainers for holding the flexible bioprocess bag uponre-translation of the supporting part to the operating position andmovement of the wall portion to the closed position.

FIGS. 1 a-1 h shows schematically different embodiments of a supporthousing in accordance with the invention. According to one embodiment ofthe invention, a support housing is provided, which comprises a sidewall and a supporting part. The support housing (hereinafter referred toas housing) may be in a vertical orientation. The side wall includes abottom wall and a side vertical wall defining together an internalvolume in an operating position. A portion of the side wall is movablebetween an open and closed position. The portion of the side wall isopened and the supporting part is translatable from an operatingposition to a bag loading position. A flexible bioprocess bag, forexample, is placed on the supporting part and is held by one or moreretainers. The flexible bioprocess bag may be capable of holdingingredients that can be mixed for getting an end product, e.g. cells.However, it may be envisioned that the flexible bioprocess bag can beused to store any ingredients, such as solutions and any fluids and ifnecessary can be mixed to form any mixture. Upon re-translating thesupporting part to the operating orientation and closing of the portionof the side wall, the flexible bioprocess bag is securely held withinthe housing. In another embodiment, the flexible bioprocess bag may be astandalone bag that can be used for storing ingredients (such assolutions and fluids). Alternatively, the flexible bioprocess bag can beplaced in any mixing tank, mixing container and so on.

In all embodiments shown in FIGS. 1 a-1 h , the side wall is shown tohave a cylindrical shape, however the geometrical design can be variedand still be covered by this invention. For example, a box shaped partof the housing and flexible bioprocess bag is feasible and rectangularwalls may be employed for construction of the bag and housing. Othershapes and geometries of the side walls and internal volumes of theflexible bioprocess bag and the housing are feasible as well ascombinations thereof, for example rectangular, triangular, hexagonal,Reuleaux triangle shaped, etc.

As shown in FIG. 1 a , a support housing 100 (hereinafter referred to ashousing 100) includes a side wall 102 and a supporting part 104according to an embodiment of the invention. The housing 100 may bevertically oriented. The housing as shown in FIG. 1 a may be at anelevated position from the ground. The side wall 102 comprises a bottomwall 106 and a side vertical wall 108. The side vertical wall 108comprises a wall portion movable between an open and closed position. Inan embodiment, the side vertical wall 108 comprises a first segment 110movable in relation to a second segment 112 between an open and a closedposition. The first segment 110 may extend throughout the height of theside wall 102. In another embodiment, the first segment may not extendthroughout the height of the side wall 102 and may extend only to aportion of side wall 102. The first segment 110 may be movably oroperably connected to the second segment 112 using different connectionmeans 114. The connection means 114 may be for example, a hingedconnection, a pivot connection, a mechanical actuator, a pneumaticactuator, an electrical actuator, a folding arm actuator and so on. Insome exemplary embodiments, the first segment can be connected to thesecond segment using a combination of different connections means. Thefirst segment 110 is moved to the open position and the supporting part104 is translatable to a bag loading position. In an embodiment, thesupporting part 104 is tiltably translatable from a vertical orientationto a horizontal orientation. For example, the supporting part 104tiltably translates or moves at an angle with respect to thelongitudinal axis ‘A’. In the horizontal orientation, the supportingpart 104 may be oriented parallel to the ground forming a tableconfiguration. The supporting part 104 is oriented at 90° angle from thelongitudinal axis ‘A’. Further, a base segment 116 of the base wall 106may be translatable to a position vertically oriented to the supportingpart 104. In another embodiment, the base segment 116 may be oriented atdifferent angles with respect to the supporting part 104. The basesegment 116 includes an opening 117 for receiving an end portion of aflexible bioprocess bag that needs to be loaded in the housing 100. Toload the flexible bioprocess bag in the housing 100, the flexiblebioprocess bag is placed on the supporting part 104 by an operator 118.This is called a loading position of the supporting part 104. Asillustrated in FIG. 1 a , the operator 118 can stand on the ground andconveniently load the flexible bioprocess bag on the supporting part 104which offers good ergonomics for the operator 118. In an embodiment, thesupporting part 104 may have a landing gear 120 that can position thesupporting part 104 in the horizontal orientation. As shown in FIG. 1 a, in an exemplary embodiment, the landing gear 120 may include twoelongated members having an end touching or resting on the ground andvertically oriented to support the supporting part 104. The landing gear120 can be folded into the supporting part 104 when not needed. In analternate embodiment, the landing gear 120 may be detachable from thesupporting part 104. Moreover, in some embodiments, the length of thelanding gear 120 can be adjusted to change the orientation and positionof the supporting part 104. More specifically, the length of each memberof the landing gear 120 can be elongated or shortened to adjust theorientation of the supporting part 104. The orientation can vary from ahorizontal orientation to any angular orientation with respect to ahorizontal plane. The landing gear 120 shown in FIG. 1 a is a mereexemplary representation, and it may be envisioned that the landing gear120 may have any other structural arrangement and can perform the samefunction of positioning the supporting part 104 in desired position.

In an embodiment, the supporting part 104 may be connected to the sidewall 102 (either the first segment 110 or the bottom wall 106) such thatthe supporting part 104 is movable in relation to the side wall 102. Thesupporting part 104 may be movably or operably connected to the sidewall 102 using different operating means. The operating means may be forexample, a hinged joint, a pivot joint, a mechanical actuator, apneumatic actuator, an electrical actuator, a folding arm actuator andso on. In some exemplary embodiments, the supporting part 104 may beconnected to the side wall using a combination of different operatingmeans. In an embodiment, the supporting part 104 may be connected to thebottom wall 106 using one or more hinge joints for example, a hingejoint 122. The hinge joint 122 is extendible as shown in FIG. 1 c . InFIG. 1 b the hinge joint 122 is in a folded or collapsed position. In anembodiment, there may be only one hinge joint connecting the supportingpart 104 to the bottom wall 106. In another embodiment, there may be twoor more hinge joints connecting the supporting part 104 to the bottomwall 106. The hinge joint 122 can be foldable and extendible as shown inFIG. 1 c . The hinge joint 122 includes two arms, such as arms 124-1 and124-2, which can move to align substantially in a straight line. Whenaligned in the straight line, the hinge joint 122 is extended to allowthe supporting part 104 to be pulled away from the housing 100. Thismakes the supporting part 104 more accessible to the user. The hingejoint 122 can be folded for pushing back the supporting part 104 intoposition, and then can be lifted to close the housing 100. Even thoughthe hinge joint 122 is shown to be foldable and extendible according toan embodiment, it can be envisioned that there can be other hinge means,for example, but not limited to, a telescopic hinge and an offset hingewhich can perform the similar function of the hinge joint 122 and can beincorporated in the housing 100 according to various embodiments withinthe scope of this disclosure.

The supporting part 104 can be positioned at different angles withrespect to a horizontal plane. In an embodiment the supporting part 104is tiltably translatable to an inclination angle less than 45° from thehorizontal plane to form the bag loading position. In anotherembodiment, the supporting part 104 may be translated to a position suchthat the supporting part 104 is at a height measuring less than 150 cmfrom the ground. The height from the ground may refer to a distancebetween an end portion 128 of the supporting part 104 and ground.However, in various embodiments, the supporting part 104 may betranslated and positioned at different angles with respect to the groundor the horizontal plane or at different heights from the ground, by theoperator 118 depending on operator's convenience. As explained earlierthe operating means facilitates the supporting part 104 to be positionedat different angles or different heights. The operating means mayinclude a functional means that enables the supporting part 104 to haltand stay at any desired angle or height without any external supportwhen translated. The functional means may be for example, a stopper, alocking unit and so on that locks the supporting part 104 at desiredposition. The operator 118 can enter the housing 100 once the supportingpart 104 and the first segment 110 are sufficiently opened to access theinterior of the housing 100. As explained earlier, the landing gear 120also provides additional support to the supporting part 104 for stayingin the desired position. The user can step on the supporting part 104and access the interior of the housing 100. When not in use, the landinggear 120 can be folded and positioned as part of the supporting part104.

The supporting part 104 may have sufficient width and length toaccommodate the flexible bioprocess bag. For example, the supportingpart 104 may have sufficient width and a curved profile to securely holdthe flexible bioprocess bag. The flexible bioprocess bag may be fastenedto the supporting part 104 by one or more retainers. The retainer may bea clipping unit, a hook and loop unit, snap fit unit, a holder, asnapping belt and so on. The retainers ensure that the flexiblebioprocess bag is securely positioned in place. However, in variousembodiments different types of retainers may be used for holding theflexible bioprocess bag on the supporting part 104.

In an embodiment, the supporting part 104 may include flap members alongits sides such a flap member 126-1 and a flap member 126-2 (i.e.retainers). The flap member 126-1 may extend along a side 129 of thesupporting part 104 and the flap member 126-2 may extend along a side130 of the supporting part 104. In an embodiment, the flap members 126-1and 126-2 may extend along only a portion of respective sides 129 and130. Once the flexible bioprocess bag is placed on the supporting part104 and laid down properly, the flap members 126-1 and 126-2 can befolded to securely position or confine the flexible bioprocess bag onthe supporting part 104. The supporting part 104 can be lifted to closethe housing 100. The flap members 126-1 and 126-2 prevent pinching ortearing of the flexible bioprocess bag by the edges of the secondsegment 112 when the supporting part 104 is moved to closing position.Once the flexible bioprocess bag is inflated, the flap members 126-1 and126-2 can be aligned such that it is properly positioned within thehousing 100. More specifically, the flap members 126-1 and 126-2 mayopen-up when the flexible bioprocess bag is inflated. In an embodiment,the flap members 126-1 and 126-2 may be made of a material that makes itflexible for opening-up and folding. Moreover, it may be envisioned thatin other embodiments, the supporting part 104 may have any otherarrangements such as, a Velcro tape, snap fit members, securing beltsand so on for securing the flexible bioprocess bag on the supportingpart 104.

The operator 118 standing on the ground can make the connections to theflexible bioprocess bag placed on the supporting part 104 (oriented inthe table configuration). This makes the bag loading process convenientfor the operator 118 resulting in better user experience. Making theconnections include but is not limited to, connecting tubes and valvesto different ports of the flexible bioprocess bag. The ports of theflexible bioprocess bag may be one or more input ports and one or moreexhaust ports which are explained in detail with respect to FIGS. 4, 6and 7 . The ports may include for example, one or more liquid ports, oneor more gas ports and one or more exhaust ports. The exhaust ports maybe provided at a top end portion of the flexible bioprocess bag, and oneor more gas ports and the liquid ports may be provided at a bottom endportion of the flexible bioprocess bag. In another embodiment, theliquid ports, gas ports and exhaust ports may be provided at the bottomend portion or bottom of the flexible bioprocess bag. However, it may beenvisioned that the liquid ports, exhaust ports and gas ports may beprovided at any portion of the flexible bioprocess bag in variousembodiments to make it convenient for loading the flexible bioprocessbag within the scope of this disclosure. Further, placing the flexiblebioprocess bag on the supporting part 104 is discussed later in thesubsequent figures. In an embodiment, the supporting part may have atube management structure for example, but not limited to channels ortrenches, for holding the tubes and connectors in order to prevententangling of these tubes or connectors. The supporting part 104 can betranslated to the vertical orientation in the housing 100, once the bagloading process is completed. This is called an operating position ofthe supporting part 104. In the operating position, the flexiblebioprocess bag is positioned within the housing 100 and oriented in avertical manner. The supporting part 104 and the first segment 110 areprovided with an interface retainer 132 and an opening 134 respectively,that enable access to input and output ports of the flexible bioprocessbag and facilitate connecting tubes to some of these ports. The inputand output ports and process of loading the flexible bioprocess bag onthe supporting part of the housing are explained in detail in laterfigures.

In an embodiment, the housing 100 may include sensor(s) for monitoringdifferent operations such as, opening and closing of the housing 100 andmovement of the supporting part 104. The sensor(s) may be arranged inthe side wall 102. The sensor(s) may be for example, but are not limitedto, proximity sensors, proximity sensors with feedback mechanism, anelectric circuit closure sensor, position sensor and force sensors. Todetect if the supporting part 104 is in a vertical orientation orhorizontal orientation or any angular orientation, a sensor 136 may beused according to an embodiment. The sensor 136 may be arranged in thesupporting part 104 to determine its angular position. When thesupporting part 104 is in the vertical orientation, the sensor 136 mayinform a control unit 138 that it is in the vertical orientation.Consequently, the housing 100 can be closed using the first segment 110.The control unit 138 controls the opening and closing of the firstsegment 110. In another embodiment, the first segment 110 may bemanually closed by the operator 118. In this embodiment, the controlunit 138 may inform the operator 118 that the supporting part 104 is inthe vertical orientation.

The housing 100 may also include a sensor for example, a sensor 140 fordetermining if the housing 100 is closed properly. The sensor 140 may bepositioned in the side wall 102 at a location closer to the firstsegment 110 when it is in the closed position. However, it may beenvisioned that one or more sensors can be arranged in any otherlocation in the housing 100. The sensor 140 can detect if an edge of thefirst segment 110 reached closer to a periphery 142 of the side wall 102to determine if the housing 100 is closed properly. In case the housing100 is not closed, the control unit 138 can inform the operator 118. Theoperator 118 can manually close the housing 100. Alternatively, thecontrol unit 138 can control movement of the first segment 110 to closethe housing 100. Even though the sensors 136 and 140 are illustrated tobe present in the housing 100, it can be envisioned that in certainembodiments, the functions performed by both these sensors can beperformed by a single sensor or multiple different sensors arranged inthe housing 100 within the scope of this disclosure.

In an embodiment, there may be sensor(s) capable of determining anyobstacles in the path of movement of the supporting part 104 and thefirst segment 110. For example, sensors 136 and 140 can act as proximitysensors to determine the presence of objects near to the supporting part104 and the first segment 110. When an object is detected in the path ofmovement of the supporting part 104 or the first segment 110, respectivesensors 136 and 140 communicate with the control unit 138 to halt theirmovement. In another embodiment, the control unit 138 may inform thepresence of obstacle, and the operator 118 can manually stop themovement of the supporting part 104 or the first segment 110. Other thana proximity sensor, others sensors used may be for example, but notlimited to, a collision detection sensor. There may be a single sensoror multiple sensors arranged in the housing 100 to determine anyobstacles or detect any collision. It may be noted that the embodimentsof the housing described in FIGS. 1 d-1 j may have similar sensors eventhough it is not explicitly described or illustrated in these figures.The control unit 138 and the sensors such as, sensors 136 and 140 cantogether form a control system.

In an embodiment, the housing 100 may include sensor(s) positioned indifferent locations to identify the position of the retainers used forsecuring the flexible bioprocess bag. For example, the sensors arearranged in the supporting part 104 such that it can determine whetherthe flap members 126-1 and 126-2 are in a folded condition or opencondition. In another example, the retainers may be snap fit memberswound around the flexible bioprocess bag placed on the supporting part104. The sensors can determine if the snap fit members are positionedaround the flexible bioprocess bag. Here the sensors used may beproximity sensors and may be arranged in the snap fit members. If thesensors determine that the snap fit members are not proximal to theflexible bioprocess bag, then it indicates that the snap fit members arenot wound around the flexible bioprocess bag. The sensors maycommunicate with the control unit 138 and inform the operator that theretainers are not properly positioned to secure the flexible bioprocessbag. In other embodiments, the different sensors such as, opticalsensor, radio frequency sensor and RFID sensor may be used to determineif the retainers are properly securing the flexible bioprocess bag onthe supporting part 104 within the scope of this disclosure.

There may be other sensors that may be capable of monitoring thedifferent steps involved in bag loading the housing 100. The stepsinclude orienting the supporting part 104 in the horizontal orientation,securing the flexible on the supporting part 104, orienting thesupporting part 104 in the vertical orientation and closing the housing100. The orientation of the supporting part 104 and the first segment110 may be determined by the sensor 136 and the sensor 140 respectively.These sensors communicate with the control unit 138 to monitor andcontrol the different steps in bag loading.

In the embodiments described in relation to FIGS. 1 d-1 j , some partsare identical to the parts of the embodiment described in FIG. 1 a-c andthose parts will have the same reference numbers and will not bedescribed in detail again.

FIG. 1 d illustrates a support housing 200 (hereinafter referred to ashousing 200) including a side wall 102 having a first segment 202 andthe second segment 112 according to an embodiment of the invention. Thefirst segment 202 is tiltably movable in relation to the second segment112 according to an embodiment. The first segment 202 may be operablyconnected to the second segment 112 using a connection means in anembodiment. The connection means in both these embodiments may be forexample, a hinged unit, a pivot unit, a mechanical actuator, a pneumaticactuator, an electrical actuator, a folding arm actuator and so on. Insome exemplary embodiments, the first segment 202 may be connected tothe second segment 112 using a combination of different connectionmeans. The first segment 202 is tiltably movable to an open position. Inan embodiment the first segment 202 may be tiltably movable to besubstantially parallel to the ground. In another embodiment, the firstsegment 202 may be aligned at an angle less than 45° with respect to thehorizontal plane. However, in other embodiments the first segment 202can be tilted at different angles with respect to the horizontal planeor the ground, by the operator 118 based on requirement. After openingthe first segment 202, a supporting part 204 can be tiltably moved tothe horizontal orientation i.e., oriented parallel to the ground. Thesupporting part 204 may rest on the first segment 202 which acts as asupport. Alternatively, the supporting part 204 may be oriented parallelto the ground as a table configuration without the support of the firstsegment 202. The first segment 202 may be oriented at different angleswith respect to the ground. The flexible bioprocess bag can be placed onthe supporting part 204 for loading in the housing 200. The supportingpart 204 and the first segment 202 are provided with an interfaceretainer 206 and an opening 208 respectively, that enable access toinput and output ports of the flexible bioprocess bag and facilitateconnecting tubes to some of these ports. The input and output ports areexplained in detail later figures.

Now, FIG. 1 e shows schematically a support housing 300 (hereinafterreferred to as housing 300) including a side wall 102 having a firstsegment 302 and the second segment 112 according to an embodiment of theinvention. The supporting part is described in FIG. 1 a-1 d as aseparate unit however in this embodiment the supporting part is integralto the first segment 302. In other words, the first segment 302 may havea same structure as the supporting part and performs the same function.The first segment 302 is tiltably translatable with respect to the sidewall 102 so that it is positioned in a horizontal orientation parallelto the ground. In an embodiment, the first segment 302 may be operablyconnected to the second segment 112 using a connection means. In anotherembodiment, the first segment 302 may be operably connected to thebottom wall 106 using another connection means. The connection means maybe for example, a hinged unit, a pivot unit, a mechanical actuator, apneumatic actuator, an electrical actuator, folding arm actuator and soon. In some exemplary embodiments, the first segment 302 can be operablyconnected to the second segment 112 or the bottom wall 106 using acombination of different connection means. In an embodiment, the firstsegment 302 may be translated to an angle less than 45° with respect tothe horizontal plane. However, in other embodiments the first segment302 can be tilted at different angles with respect to the horizontalplane or the ground, by the operator (e.g. the operator 118) based onthe operator's convenience. The connection means may include afunctional means that enables the first segment 302 to halt and stay atany desired angle with respect to the ground or the horizontal planewithout any external support when translated. The functional means maybe a stopper, a locking unit and so on that locks the first segment 302at desired position.

The flexible bioprocess bag is placed on the first segment 302. Thefirst segment 302 may have flap members similar to that explained inconjunction with FIG. 1 a even though not illustrated in FIG. 1 e forsecurely positioning or confining the flexible bioprocess bag on thefirst segment 302. In another embodiment, there may be retainers thathelp in securely positioning the flexible bioprocess bag on the firstsegment 302. Moreover, as illustrated in FIG. 1 e , the first segment302 may have sufficient width for securely holding the flexiblebioprocess bag. The first segment 302 can be retranslated to a verticalorientation so that the flexible bioprocess bag is positioned within thehousing 300.

A portion of the bottom wall 106 may be also movable to a verticalorientation or towards a vertical plane. As illustrated in FIG. 1 e , abase segment 304 represents the portion of the bottom wall 106. In anembodiment, the base segment 304 is connected to the first segment 302such that the base segment 304 also moves along with the first segment302. For example, the base segment 304 is fixed to the first segment302. Alternatively, the base segment 304 and the first segment 302 forma single unit. Thus, when the first segment 302 is translated to aposition parallel to the ground or aligned to the horizontal plane, thebase segment 304 may align to a vertical plane. The first segment 302and the base segment 304 may form an L-shaped configuration. In otherwords, the base segment 304 may be aligned at an angle less than orequal to 90° or greater than 90° with respect to the first segment 302.It may be envisioned that the base segment 304 may be aligned atdifferent angles with respect to the first segment 302 according to someembodiments. The base segment 304 includes a mating retainer 306. Theflexible bioprocess bag can have an end connected to the mating retainer306. The mating retainer 306 provides assistance in positioning orretaining the flexible bioprocess bag within the housing 300. This isfurther explained in conjunction with FIGS. 2 and 3 . The first segment302 is operatively connected to the base segment 304 using an operatingmeans such as the operating means 122 in the housing 100 even though itis not illustrated in FIG. 1 e . The operating means may be extendableas shown in FIGS. 1 a-c , to enable the first segment 302 to be pulledout from the housing 300 so that the flexible bioprocess bag can beplaced on the first segment 302. The first segment 302 can be pushedback and then translated to a vertical position for closing the housing300. Such an operating means enables the first segment 302 to movefurther away from the housing 300 thereby making it convenient for theuser to load the flexible bioprocess bag. The first segment 302 includesan interface retainer 308 for connecting to an interface plate of theflexible bioprocess bag. Connecting the interface plate to the interfaceretainer 308 assists in the holding the flexible bioprocess bag on thefirst segment 302 (i.e. supporting part).

In an embodiment, a base segment is operably connected to a firstsegment. As schematically illustrated in FIG. 1 f , a base segment 400is tiltably movable with respect to the first segment 302. The basesegment 400 may be operably connected to the first segment 302. The basesegment 400 may also include a mating retainer 402, similar to theinterface retainer 308 in the housing 300, for performing the samefunction. In an embodiment, the base segment 400 is operably connectedto the first segment 302 using an operating means, such as but notlimited to, a hinged unit, a pivot unit, a mechanical actuator, apneumatic actuator, an electrical actuator, a folding arm actuator andso on. In some exemplary embodiments, the base segment 400 can beoperably connected to the first segment 302 using a combination ofdifferent operating means. The base segment 400 may be oriented at anangle equal to 45° with respect to a horizontal axis 404. However, thebase segment 400 can be positioned at different angles with respect tothe first segment 302. During bag loading, the base segment 400 can bepositioned at different angles for placing the flexible bioprocess bagon the first segment 302 and connecting to the base segment 400. Thebase segment 400 may be re-translatable to be parallel to the ground oraligned to the horizontal axis 404. During operation after loading theflexible bioprocess bag, the first segment 302 is moved to a verticalorientation. Simultaneously, the base segment 400 also moves to ahorizontal orientation or aligns to the horizontal axis 404 along withthe first segment 302. In another embodiment, the base segment 400 isindependently movable parallel to the horizontal axis 404 by theoperator.

In the housings shown in FIGS. 1 a-f , the flexible bioprocess bag canbe placed on the supporting part. A first end of the flexible bioprocessbag may be connected to an upper edge of the supporting part and asecond end of the flexible bioprocess bag may be connected to the basesegment of the housing. When the housing is closed, the flexiblebioprocess bag remains connected to the upper edge and the base segment,for it to be positioned within the housing.

FIG. 1 g schematically illustrates a support housing 500 (hereinafterreferred to as housing 500) having a first segment 502 that iscollapsible according to an exemplary embodiment. The first segment 502may be collapsible and extendable in a longitudinal direction. In anembodiment, the first segment 502 is tiltably movable with respect tothe second segment 112. The first segment 502 can be collapsed and thentiltably moved to position it substantially parallel to the horizontalplane. Thereafter, the first segment 502 can be extended to form a bagloading support surface. In an exemplary embodiment as illustrated inFIG. 1 g , the first segment 502 may have a first portion 504 and asecond portion 506. The first portion 504 may slide with respect to thesecond portion 506 to collapse the first segment 502. The first portion504 may have a sliding unit and the second portion 506 may have asliding rail (not shown in FIG. 1 g only for ease of representation) inan exemplary embodiment. The sliding unit may run through the slidingrail enabling the first portion 504 to slide over the second portion506. In other embodiments, there can be any other arrangements thatfacilitate the sliding movement or collapsing movement of the firstportion 504 over the second portion 506. In an embodiment a retainer 508may be used to move the first portion 504 slidably over the secondportion 506. The collapsed first segment 502 can be tiltably moved to bearranged parallel to the horizontal plane. Thereafter, the first portion504 can be slid again over the second portion 506 to extend the firstsegment 502 to attain a bag loading position. Here, the first segment502 acts as the supporting part for holding the flexible bioprocess bagon it. Even though, the first segment 502 is discussed to have twoportions which can collapse, it may be envisioned that the first segment502 can have more than two portions which can collapse in different waysand then extend to form a table like configuration enabling the operatorto load the flexible bioprocess bag standing on the ground in variousexemplary embodiments. The housing 500 includes a bottom wall 510 havinga portion i.e., a base segment 512 which is operably coupled to thefirst segment 502. The base segment 512 may be operably connected to thesecond portion 506. The base segment 512 includes a mating retainer 514.The second portion 506 of the first segment 502 includes an interfaceretainer 516.

FIG. 1 h schematically illustrates a support housing 600 (hereinafterreferred to as housing 600) having a first segment 602 comprising afirst portion 604 and a second portion 606, according to an embodimentof the invention. The first portion 604 and the second portion 606 mayslide over the second segment 112 to open the housing 600 as illustratedin FIG. 1 h . The first portion 604 and the second portion 606 may slideseparately in a transverse direction. The second segment 112 may haveone or more sliding rails and the first portion 604 and the secondportion 606 may have respective sliding units that slide overcorresponding sliding rails to facilitate the sliding movement. Further,in an embodiment, sliding rails and sliding units may be provided alonga periphery of the first portion 604 and the second portion 606 toenable movement between these two portions. However, it may beenvisioned that the first portion 604 and the second portion 606 can bearranged in different configurations and opened in multiple differentways according to various exemplary embodiments of the invention. Oncethe housing 600 is opened, a supporting part 608 may be tiltably movedto form a table configuration. In the table configuration as describedearlier, the supporting part 608 is positioned parallel to the ground oraligned to a horizontal plane. The supporting part 104 may include aholding means 610.

FIG. 1 i schematically illustrates a support housing 700 (hereinafterreferred to as housing 700) having a first segment 702 comprising afirst portion 704, a second portion 706 and a third portion 708according to an embodiment of the invention. As illustrated, the firstportion 704 is movable between an open and closed position in atransverse direction. The first portion 704 may be operably connected tothe second segment 112 using a connection means such as for example, ahinged connection, a pivot connection, a mechanical actuator, apneumatic actuator, an electrical actuator, folding arm actuator and soon. The connection means is not illustrated in FIG. 1 i only for sakeconvenience of representation. In some exemplary embodiments, the firstsegment can be connected to the second segment using a combination ofdifferent connections means. The second portion 706 may slide over thethird portion 708 to open the housing 700. The second portion 706 andthe third portion 708 may slide separately. The third portion 708 mayhave a sliding rail on it and the second portion 706 may have a slidingunit (not shown in FIG. 1 i only for ease of representation) in anexemplary embodiment. The sliding unit may run through the sliding railso that the second portion 706 slides over the third portion 708. Inother exemplary embodiments, there can be any other arrangements thatfacilitate the sliding movement or collapsing movement of the secondportion 706 over the third portion 708. It may be envisioned that thefirst portion 704, the second portion 706 and the third portion 708 canbe arranged in different configurations and thereby opened in multipledifferent combinations in various embodiments of the invention. It maybe noted that the housing shown in different embodiments from FIGS. 1a-e and FIGS. 1 g-h can have a retainer similar to the housing 600 ofFIG. 1 f according to various embodiments, but is not illustrated inthese figures. The housing 700 includes a bottom wall 710 having aportion i.e. a base segment 712 which is operably coupled to the firstsegment 702. The base segment 712 may be operably connected to the thirdportion 708. The base segment 712 includes a mating retainer 714. Thethird portion 708 includes an interface retainer 716 which can receivean interface plate of a flexible bioprocess bag positioned within thehousing 700.

FIG. 1 j illustrates a support housing 800 (hereinafter referred to ashousing 800) having a first segment 802 comprising a first portion 804and a second portion 806 according to an exemplary embodiment of theinvention. The first segment 802 may be collapsible and extendable in alongitudinal direction. In an embodiment, the first segment 802 istiltably movable with respect to the second segment 112 to positionparallel to the horizontal plane. Thus, the first segment 802 forms abag loading support surface. In an exemplary embodiment as illustratedin FIG. 1 g , the first segment 802 may have a first portion 804 and asecond portion 806. The first portion 804 may slide with respect to thesecond portion 806 to collapse the first segment 802. The first portion804 may have a sliding unit and the second portion 806 may have asliding rail (not shown in FIG. 1 g only for ease of representation) inan exemplary embodiment. The sliding unit may run through the slidingrail enabling the first portion 804 to slide over the second portion806. In other embodiments, there can be any other arrangements thatfacilitate the sliding movement or collapsing movement of the firstportion 804 over the second portion 806. In an embodiment a retainer 808may be used to move the first portion 804 slidably over the secondportion 806. The collapsed first segment 802 can be tiltably moved to bearranged parallel to the horizontal plane. Thereafter, the first portion804 can be slid again over the second portion 806 to extend the firstsegment 802 to a bag loading position. Even though, the first segment802 is discussed to have two portions which can collapse and extend, itmay be envisioned that the first segment 802 can have more than twoportions which can collapse in different ways and then extend to form atable like configuration enabling the operator to load the flexiblebioprocess bag standing on the ground in various exemplary embodiments.

The housing 800 includes a bottom wall 810 having a portion i.e. a basesegment 812 which is operably coupled to the first segment 802. The basesegment 812 may be operably connected to the second portion 806. Thebase segment 812 includes a mating retainer 814. The second portion 806includes an interface retainer 816 which can receive an interface plateof a flexible bioprocess bag positioned within the housing 800.

Further it may be noted that the side walls of the housing illustratedin FIGS. 1 a-1 j may have a jacket configuration carrying liquids fortransferring heat to ingredients in the flexible bioprocess bagaccording to an embodiment. The liquids flowing through the housing maybe hot and may transfer appropriate heat to the ingredients. In anembodiment, the temperature of the liquids can be controlled so thatdesired heat is only transferred to the ingredients. In otherembodiments, the side wall of the housing illustrated in FIGS. 1 a-1 jmay have heating coil as an integral part of the side wall for heatingthe ingredients. The heating coil is controlled so that only desiredamount of heat is only transferred to the ingredients in the flexiblebioprocess bag.

Turning now to FIG. 2 illustrating a mixing system 900 capable ofholding fluid and other ingredients and mixing the fluid and theingredients according to an embodiment. The mixing system 900 includes aflexible bioprocess bag 902, which can be for example, a flexiblebioprocess bag used in a single use bioreactor. The flexible bioprocessbag 902 according to the invention may be used with a mixing unit 904.The mixing unit 904 may be, for example, a fan shaped mixer, a magneticimpeller, an impeller unit and so on. The mixing unit 904 may bearranged at a bottom portion of the flexible bioprocess bag 902. Inanother embodiment, the mixing unit 904 may be arranged at a side bottomportion of the flexible bioprocess bag 902. However, it may beenvisioned that the mixing unit 904 may be positioned at any otherposition at the bottom end portion of the flexible bioprocess bag 902which would enable efficient mixing of the content according to variousembodiments of the invention. Mixing of the fluids and contents isessential to enable proper interaction between the contents for furtherdevelopment of cell cultures. During the cell growth process, the fluidsin the mixing bag (e.g. for a bioprocess application) must also beagitated in order to maintain uniform distribution of temperature, gasesand nutrients. The flexible bioprocess bag 902 can be loaded into any ofthe housings illustrated in FIGS. 1 a -1 i.

The operator needs to load the flexible bioprocess bag in the housingand the content needs to be filled in the bag. There are severalchallenges in loading the bag, however in the disclosed housing, as theflexible bioprocess bag is loaded at ground level (i.e. the operator canplace the bioprocess in the housing while standing on ground) theloading process is more convenient.

Now moving to FIG. 3 , the flexible bioprocess bag 902 can be placed ona supporting part 1000 in the table configuration for loading accordingto an exemplary embodiment. A first end portion 906 is connected to abase segment 1004 and a second end portion 908 of the flexiblebioprocess bag 902 can be connected to a retainer 1002. The first endportion 906 is opposite to the second end portion 908. The flexiblebioprocess bag 902 is connected to the retainer 1002 in a simple mannerfor illustrative purpose as shown in FIG. 3 therefore there may bedifferent ways to connect the flexible bioprocess bag to the retainer1002 in various exemplary embodiments. In an exemplary embodiment, theflexible bioprocess bag 902 may have a mating retaining member that canbe connected to the retainer 1002. The mating retaining member may beprovided in the second end portion 908 and slid into any slot providedin the retainer 1002. In another embodiment, the mating retaining membermay be snap fitted to the retainer 1002. The supporting part 1000 mayhave retainers positioned along its sides for holding the flexiblebioprocess bag 902 in place. In an embodiment, the supporting part 1000may have flap members along the sides similar to the housing 100 of FIG.1 a . These flap members act as retainers to confine the flexiblebioprocess bag on the supporting part 1000. The flexible bioprocess bag902 may have the mixing unit 904 at the first end portion 906. Themixing unit 904 is operably connected to a drive unit 1006 arranged atthe base segment 1004. In an embodiment, the drive unit 1006 is anintegral part of the base segment 1004. In another embodiment, the driveunit 1006 may be a separate unit that can be arranged to be held by thebase segment 1004. For example, the base segment 1004 may include amating retainer 1008 for receiving the drive unit 1006. The matingretainer 1008 may be a normal slit or an opening that can hold the driveunit 1006 according to an embodiment. Alternatively, the mating retainermay be a functional or operational unit that receives and facilitatesthe operation of the drive unit 1006. The base segment 1004 is tiltablymovable with respect the supporting part 1000. The base segment 1004 canbe oriented in a vertical manner or in other words, the base segment1004 is positioned substantially perpendicular to the supporting part1000. While loading the flexible bioprocess bag, the mixing unit 904 isconnected to the drive unit 1006 thereby connecting to the base segment1004. The supporting part 1000 is translated to a vertical orientationpositioning the flexible bioprocess bag 902 in a vertical orientation.The base segment 1004 also moves to align with the horizontal plane. Thebase segment 1004 and the supporting part 1000 are independentlymovable. In the vertical orientation, the first end portion 906 is heldor supported by the base segment 1004. Further, the retainer 1002 alsoensures that the flexible bioprocess bag 902 remains in the verticalorientation. During operation, liquids such as, buffer, base and otherliquid contents may be fed into the flexible bioprocess bag 902 throughthe liquid port(s). The liquid port(s) may be connected to feed tubeswhich can be guided through one or more tube management structures (suchas trenches) provided in the supporting part 1000 or a first segment ofthe housing or in the retainer 1002. The gases needed for contents inthe flexible bioprocess bag 902 are fed through the gas port(s). Theremay be exhaust gases that gets generated and needs to be directed outthrough exhaust port(s). The liquid port(s), gas port(s) and the exhaustport(s) may be located at a top end portion or bottom end portion or anyother portion of the flexible bioprocess bag 902 which is convenient forloading the flexible bioprocess bag according to various embodiments.These ports are not shown in FIG. 3 only for sake of convenience ofrepresentation, and hence the flexible bioprocess bag 902 may havemultiple ports which are explained in detail in conjunction with FIG. 4. While loading, the tubes and other required units are connected to theexhaust port(s) and gas port(s) at ground level which makes itconvenient for the user by avoiding the need for climbing to a heightfor accessing the top portion of the housing.

FIG. 4 illustrates the mixing system 900 according to an exemplaryembodiment. Hereinafter FIG. 4 is explained along with FIGS. 5 a-e todescribe an exemplary way of loading the flexible bioprocess bag 902 ina support housing 1100 (hereinafter referred to as housing 1100). Theflexible bioprocess bag 902 includes the first end portion 906 and thesecond end portion 908. The flexible bioprocess bag 902 includes one ormore liquid port(s) such as, a liquid port 910-1 and a liquid port910-2, one or more gas port(s) such as, a gas port 912-1 and a gas port912-2 at the first end portion 906. The liquid ports 910-1 and 910-2 areused for supplying liquids into the flexible bioprocess bag 902. Theliquids may include for example, buffers, base, culture medium and serumwhich facilitate cell growth in the flexible bioprocess bag 902. The gasports 912-1 and 912-2 are used to supply different gases such as but notlimited to, oxygen, carbon dioxide and nitrogen into the flexiblebioprocess bag 902. For better cell growth certain concentration ofdissolved oxygen and other gases must be maintained. It may be notedthat only two gas ports (such as, gas ports 912-1 and 912-2) and twoliquid ports (such as, liquid ports 910-1 and 910-2) are shown to bepresent in the flexible bioprocess bag 902, however there can be morethan two gas ports or more than two liquid ports in the flexiblebioprocess bag 902 according to different exemplary embodiments. In analternative embodiment, gas ports and/or liquid ports and respectivelines are connected to the first end portion of the bag 902. In analternate embodiment, the flexible bioprocess bag 902 may have only oneliquid port and one gas port.

Another efficient way of introducing gases into the flexible bioprocessbag 902 is sparging, which involves forming bubbles in the liquids.These bubbles have large surface to volume ratio and hence dissolvesmore quickly than large size bubbles. A sparger 914 (also called asparging unit) may be positioned at the first end portion 906 proximalto the gas ports 912-1 and 912-2, and liquid ports 910-1 and 910-2. Inan alternate embodiment, only one sparger for example, the sparger 914may be present for supplying gases into the flexible bioprocess bag 902and there may not be any gas ports such as, the gas ports 912-1 and912-2. Further, it may be also envisioned that the flexible bioprocessbag such as, the flexible bioprocess bag 902 may include more than onesparger for supplying different gases within the scope of thisdisclosure. These spargers may be located at different portions of theflexible bioprocess bag, so as to enable efficient mixing of the gasesalong with other contents for cell growth. In another embodiment, asparger may be an integral part of the mixing unit 904. Alternatively,the sparger may be located in the receiver 1008 of the base segment 1004(illustrated in FIG. 3 ) proximal to the mixing unit 904. Alternatively,the gas ports such as, the gas ports 912-1 and 912-2 may be arrangedproximal to the mixing unit 904.

As different gases and liquids are added into the flexible bioprocessbag 902 there is a need to frequently measure different parameters thataffect the growth of cells. The concentration of the gases and liquidscan influence the cell growth rate. Hence, one or more sensors forexample, a sensor 916-1 and a sensor 916-2 may be provided at the firstend portion 906 of the flexible bioprocess bag 902. The sensor 916-1 andthe sensor 916-2 may be used to measure different parameters. Theparameters may be for example, oxygen level, nitrogen level, carbondioxide level, buffer level, base level, cell growth level, cell deathand so on. Each of these parameters may have associated parameterthresholds. Thus, the sensors 916-1 and 916-2 may determine whetherparameters are within their respective thresholds. The sensors hencefacilitate in frequently monitoring the cell growth in the flexiblebioprocess bag and maintaining all desired parameters. Even though, onlytwo sensors are shown to be present in the flexible bioprocess bag 902,there may be more than two sensors or only one sensor depending on thedifferent parameters that need to be monitored according to variousother embodiments within the scope of this disclosure. In an embodiment,the liquid ports (such as, the liquid port 910-1 and the liquid port910-2), the gas ports (such as, the gas port 912-1 and 912-2) and thesensor ports (such as, the sensor port 916-1 and the sensor port 916-2)are held in an interface plate 918. The interface plate 918 may have alid 919 which covers it and can be opened. The lid 919 may open as shownin FIG. 4 according to an embodiment; however it may be envisioned thatin other embodiments, the lid may be collapsible to stay on the flexiblebioprocess bag 900 or may be removed from the interface plate 918.

During cell culture process, there can be unnecessary gases (i.e.exhaust gases) than need to be expelled out from the flexible bioprocessbag 902. The flexible bioprocess bag 902 includes an exhaust port 920that expels the exhaust gases from the flexible bioprocess bag 902. Theexhaust port 920 may be positioned at the second end portion 908. Theflexible bioprocess bag 902 is shown to include only one exhaust port920 however there can be more than one exhaust port in the flexiblebioprocess bag 902 according to other embodiments. The exhaust ports maybe arranged at the second end portion 908 or the first end portion 906or any other portion of the flexible bioprocess bag 902 based onconvenience of expelling exhaust gases. The flexible bioprocess bag 902can also include a gas port 922 at the first end portion 906. The gasport 922 allows gas to be fed into the flexible bioprocess bag 902. Inan embodiment, the gas port 922 and the exhaust port 920 may be part ofa mating retaining member. The mating retaining member can be connectedto the retainer 1002. The mating retaining member may be fastened orconnected to the retainer 1002 in multiple different ways according tovarious embodiments. In an alternate embodiment, the mating retainingmember having the ports (such as one or more gas ports and one or moreexhaust ports) may be connected to a top end portion of a supportingpart of a housing, for example, a housing 100, 200, 300, 400, 500, 600,700 and 800 illustrated in FIGS. 1 a-j . The top end portion may have acoupling unit or a snapping unit for coupling or snapping the matingretaining member on to the supporting part. However, it may beenvisioned that the top end portion may have any other connecting unitfor connecting the mating retaining member to the supporting part andwhich can be disconnected when required by the operator to remove theflexible bioprocess bag according to various other embodiments.

Now the process of loading the flexible bioprocess bag 902 in thehousing 1100 is illustrated in FIGS. 5 a-e . The operator 118 may carrythe flexible bioprocess bag 902 arranged in a collapsed configurationaccording to an embodiment. The operator 118 places the flexiblebioprocess bag 902 on a supporting part 1102 as shown in FIG. 5 a . Theflexible bioprocess bag 902 may be in a collapsed configuration whenplaced on the supporting part 1102 according to an embodiment. Differentpatterns and schemes of folding or rolling the bag may be employed. Inan embodiment, as shown in FIG. 5 b-e , the flexible bioprocess bag 902may be folded in a Z-shaped manner. In another embodiment the flexiblebioprocess bag 902 may be arranged in a rolled or reel configuration.However, it may be envisioned that the flexible bioprocess bag can berolled or folded in various patterns, such as but not limited to,horizontally, vertically, diagonally, any different combinations,multiple folds, repetitive folded manner and so on.

The collapsed configuration enables the operator to conveniently placethe flexible bioprocess bag 902 on the supporting part 1102. Thesupporting part 1102 includes an interface retainer 1104. The operator118 unfolds the flexible bioprocess bag 902 as shown in FIG. 5 b . Theinterface plate 918 (shown in FIG. 4 is not shown in FIG. 5 a-e ) havingmultiple ports is positioned in the interface retainer 1104. In anembodiment, the interface plate 918 may be arranged or slid into a slotin the interface retainer 1104 so that it is securely positioned inplace on the supporting part 1102. In another embodiment, the interfaceplate 918 may be snap fitted into a slot in the interface retainer 1104.Then for removing the flexible bioprocess bag, the snap fit connectioncan be released to disconnect the interface plate 918 from the interfaceretainer 1104. It may be envisioned that the interface plate 918 can besecurely positioned in the interface retainer 1104 using any othercoupling mechanism or connecting mechanism without deviating from thescope of this disclosure. Few exemplary embodiments of the opening (e.g.the interface retainer 1104) are described with conjunction to FIG. 8 .

The mixing unit 904 is connected to a drive unit (for example thedriving unit 1002) arranged in a base segment 1106 as shown in FIG. 5 c. The driving unit is arranged in a mating retainer 1110 of the basesegment 1106 (shown in FIG. 5 a ). The base segment 1106 providesadditional support for positioning the flexible bioprocess bag 902 onthe supporting part 1102. The second end portion 908 of the flexiblebioprocess bag 902 is connected to a retainer 1108 as illustrated inFIG. 5 d . The retainer 1108 holds the flexible bioprocess bag 902 inposition on the supporting part 1102. The retainer may be designed invarious configurations and the shown example is only schematic. Theretainer may be designed as a single rod, plate or as a plate covering alarger or substantially the total top surface of the vessel and bag. Theretainer 1108 may not be rigid, but have a hinged, (un-foldable) ortelescopic design and may support multiple functions of holding andfasten other components than the bag itself. The retainer 1108 may alsofacilitate in unfolding the flexible bioprocess bag 902. For example,the flexible bioprocess bag 902 may be in the roll or reel configurationaround a roller member. An end portion of the flexible bioprocess bag902 may be attached to the roller member and the bag may be rolledaround the roller member. The ends of the roller member may be connectedto the retainer 1108 and the mixing unit 904 is connected to the matingretainer 1110. The retainer 1108 can move along the supporting part 1102(even though not shown in FIG. 5 a-e but illustrated in FIG. 8 a ), toroll the roller member so that flexible bioprocess bag 902 unfolds onthe supporting part 1102. Here there is not user assistance needed forunfolding or unrolling the flexible bioprocess bag 902. Alternatively,the roller member can be rolled manually by the user to unfold theflexible bioprocess bag and then roller member can be removed. When theflexible bioprocess bag is rolled there can be reduced mechanical stressor material failure and crack as compared to being folded.

Further, the supporting part 1102 may include other retainers (not shownin FIGS. 5 a-e ) that may be used to fasten the flexible bioprocess bag902 and hold it in place according to another embodiment. In anotherembodiment, the supporting part 1102 may have flap members along itssides for securely positioning the flexible bioprocess bag 902. The flapmembers are described in conjunction with FIGS. 1 a-c . The matingretainer 1110 of the base segment 1106 may also receive the sparger orsparging unit 914 according to an embodiment. The mating retainer 1110enables the sparger 914 to be in place on the supporting part 1102 andalso adds to the support for the flexible bioprocess bag 902. The matingretainer 1110 may also have the drive unit which can get connected tothe mixing unit 904 as explained earlier. In another embodiment, thesparger 914 may be placed in another mating retainer (not shown in FIG.5 a-e ) provided in the base segment 1106. The housing 1100 can beclosed by the operator 118 by moving the supporting part 1102 to avertical position as illustrated in FIG. 5 e . Before closing thehousing 1100, a landing gear 1112 can be collapsed or folded into thesupporting part 1102. In another embodiment, the landing gear 1112 canbe disconnected from the supporting part 1102.

While placing the flexible bioprocess bag 902, in an exemplaryembodiment, the interface plate 918 may be positioned in the slot of theinterface retainer 1104, such that the liquid ports 910-1 and 910-2, thegas ports 912-1 and 912-2 and the sensors 916-1 and 916-2 can projectout through the holding means 1104. FIG. 6 illustrates the liquid ports910-1 and 910-2, the gas ports 912-1 and 912-2 and the sensors 916-1 and916-2 projecting out from the interface retainer 1104. In anotherembodiment, the interface retainer 1104 may be arranged at any otherlocation on the supporting part 1102 and accordingly the liquid ports910-1 and 910-2, the gas ports 912-1 and 912-2 and the sensors 916-1 and916-2 may be configured in the flexible bioprocess bag 902 so as toalign with the interface retainer 1104. The interface plate 918positioned in the interface retainer 1104 also provides additionalassistance in placing the flexible bioprocess bag 902 in place. Theinterface plate 918 may be configured to include additional ports orlesser number of ports (such as liquid ports, exhaust ports, gas portsand sensor ports) based on the requirement of the application (forexample a bioprocess application) in other embodiments within the scopeof this disclosure.

When the supporting part 1102 is in the table configuration, theoperator 118 can connect a gas tube (i.e. a gas tube 1114) to the gasport 922. The gas tube 1114 may be connected to respective gasreservoirs for supplying gas into the flexible bioprocess bag 902. Inanother embodiment, when the supporting part 1102 moves to the operatingposition, the gas tube 1114 connects to the gas port 922 without userassistance, once the flexible bioprocess bag 902 is unfolded to retainon the supporting part 1102. The gas tube 1114 may be attached to thesupporting part 1102 by a fastening member 1116 according to anembodiment. Alternatively, the flexible bioprocess bag 902 may unfoldafter the supporting part 1102 is moved to the operating position andsubsequently the gas tube 1114 gets connected to the gas port 922without any user assistance. In this embodiment, the gas tube 1114 maybe already attached to the supporting part 1102. Another way in which agas tube is attached to the supporting part is described in conjunctionwith FIG. 10 . Even though only one tube is shown FIG. 6 , there can bemore than one tube that may be connected to different ports such as,liquid ports and gas ports according to various embodiments within thescope of the disclosure. Further, the operator 118 may also connectexhaust filter(s) to the exhaust port 920. The operator 118 is able toload the flexible bioprocess bag 902 and make connections to the liquidports, the exhaust ports, the gas ports and the sensor ports whilestanding on the ground thereby providing good ergonomics and userexperience. In an alternate embodiment, the exhaust port 920 and the gasport 922 (as shown in FIGS. 4 and 6 ) may be arranged in a single unit(as a mating retaining member) for example, a manifold, and connected tothe retainer 1108. Once the flexible bioprocess bag 902 is loaded, thesupporting part 1102 is translated to vertical orientation to close thehousing 1100. Here, the flexible bioprocess bag 902 is placed within thehousing 1100. After completion of cell culture process, the contents ofthe flexible bioprocess bag 902 may be removed. Thereafter, thesupporting part 1102 can be translated to the table configuration (i.e.the supporting part 1102 is positioned parallel to the ground), and thentubes and other connections can be disconnected. The flexible bioprocessbag 902 can be removed from the supporting part 1102 conveniently by theoperator to complete the unloading process.

For ports and lines introducing fluid into the volume and internal ofthe bag, check valve arrangements may be applied to avoid any drainingor backflow of reactor fluid into the lines. The check valves may bearranged in the line upstream the connection to the bag, at theconnection of the bag or inside the bag at the outlet of the connectingline, tube or port which is known and disclosed in US2016/0194592, whichis hereby incorporated by reference in its entirety. For example, ifliquids are fed into the flexible bioprocess bag 902 from the bottom,there is a need to ensure that there is no back flow of the liquids.FIG. 7 illustrates the liquid port 910-1 according to an embodiment. Asthe liquid port 910-1 is arranged at the first end portion 906, theliquid filled in the flexible bioprocess bag 902 may flow back outward.The liquid port 910-1 includes a check valve 1200 that restricts theoutward flow of liquid from the flexible bioprocess bag 902. The checkvalve 1200 only allows inward flow of the liquid thus prevents any lossof liquid from the flexible bioprocess bag 902. Similarly, the liquidport 910-2 may also have a check valve similar in structure andconfiguration of the check valve 1200. Further, it may be envisionedthat the liquid port may have any other structural component thatprevents the outward flow of the liquid other than a check valveaccording to other embodiments within the scope of this disclosure.

FIG. 8 a illustrates a support housing 1300 (hereinafter referred to ashousing 1300) for holding a flexible bioprocess bag according to anembodiment. The housing 1300 includes a first segment 1302 operativelyconnected to a second segment 1304. The first segment 1302 tiltablyopens to access the interior of the housing 1300. The operator 118 canplace the flexible bioprocess bag on the first segment 1302 which actsas a supporting part. The first segment 1302 includes flap members1306-1 and 1306-2 along its sides which act as retainers. Once theflexible bioprocess bag is placed on the first segment 1302 and laiddown properly, the flap members 1306-1 and 1306-2 can be folded tosecurely position or confine the flexible bioprocess bag on the firstsegment 1302. A second end portion of the flexible bioprocess bag mayneed to be connected to a retainer 1308. The flexible bioprocess bag mayhave a first end portion that needs to be connected to a base segment1310. In order to connect, the flexible bioprocess bag needs to beunfolded to some extent by the operator 118. The retainer 1308 can bemoved along a track 1312. In an embodiment, the track 1312 may be in theform of a sliding rail, and the retainer 1308 may have a sliding unitthat enables it move along the track 1312. The operator 118 can connectthe second end portion of the flexible bioprocess bag to the retainer1308 and it can be moved to a position at an end portion 1314 of thefirst segment 1302. The track 1312 or the retainer 1308 may include alocking unit that can halt the movement of the retainer 1308 in thetrack 1312. The locking unit can position the retainer 1308 at anydesired position in the track 1312. In an alternate embodiment, themovement of the retainer 1308 along the track 1312 can be controlled bya control unit (for example, the control unit 138 shown in FIG. 1 a .Once the retainer 1308 moves, it unfolds the flexible bioprocess bag(e.g. the flexible bioprocess bag 900) along the first segment 1302.Considering the bag arrangement illustrated in FIGS. 5 b-e , theretainer 1308 can unfold the flexible bioprocess bag folded in theZ-shaped manner. The flexible bioprocess bag may be unfolded when thefirst segment 1302 is in the table configuration or in the operatingposition. It may be noted that the structure of the retainer 1308illustrated here is according to one embodiment, and the retainer 1308can have any other structural configuration or arrangement in otherembodiments within the scope of this disclosure.

The first segment 1302 includes an interface retainer 1316 for receivingan interface plate of the flexible bioprocess bag (for example, theinterface plate 918 of the flexible bioprocess bag 902. The base segment1310 includes a mating retainer 1318 for holding a drive unit whichdrives a mixing unit in the flexible. This is explained in detailearlier.

The interface retainer 1316 may include a shutter 1320 that can move toincrease the size of the interface retainer 1316. The operator (such asthe operator 118) can insert the interface plate within the interfaceretainer 1316 while placing the flexible bioprocess bag 902 on the firstsegment 1302. The second end portion of the flexible bioprocess bag 902is connected to the base segment 1310 through the mating retainer 1318.When the first end portion of flexible bioprocess bag 902 is connectedto the retainer 1308, the shutter 1320 can be moved to widen theinterface retainer 1316.

In another embodiment as shown in FIG. 8 b , the interface retainer 1316can include two shutters, the shutter 1320 and the shutter 1322. Theoperator may insert the interface plate of the flexible bioprocess bag902 in the interface retainer 1316. The size of the interface retainer1316 can be varied by moving the shutters 1320 and 1322. Whileconnecting the first end portion 906 of the flexible bioprocess bag 902to the base segment 1310, the shutter 1322 may be in a collapsed stateand the shutter 1320 may remain in the drawn-out state. When the secondend portion 908 is connected to the retainer or a top end portion of thesupporting part, the shutter 1320 may be moved to a collapsed state andthe shutter 1322 may move to the drawn-out state. The movement of theshutters 1320 and 1322 may be controlled by the operator or it may beautomatically controlled for example, by the control unit 138. Thus, thesize of the interface retainer 1316 can be varied based on therequirement.

In an embodiment as illustrated in FIG. 8 c , the interface retainer1316 may be capable of moving in the first segment 1302. As illustratedthere are two shutters 1324 and 1326 provided at two sides of theholding means 1316. These shutters can move between a collapsed anddrawn-out sate. The operator can position the interface plate in theinterface retainer 1316, and when connecting the second end portion ofthe flexible bioprocess bag 902 to the retainer 1308 the shutter 1326can change from the drawn-out state to the collapsed state therebymoving the interface retainer 1316. The operator may connect the firstend portion of the flexible bioprocess bag 902 to the base segment 1310through the receiver 1318, then the shutter 1324 can change from thedrawn-out state to the collapsed state thereby moving the interfaceretainer 1316. Here, the shutter 1326 moves from the collapsed state tothe drawn-out state. As the interface retainer 1316 moves, it helps theoperator in conveniently loading the flexible bioprocess bag 902 on thefirst segment 1302. Even though, few embodiments of the structuralconfiguration of the interface retainer 1316 is illustrated in FIGS. 8a, 8 b and 8 c , it may be envisioned that the interface retainer 1316can have different structural arrangements for conveniently receivingthe interface plate to aid bag loading, within the scope of thisdisclosure as there are numerous embodiments and alternatives tomentioned shutter mechanism to achieve the desired positioning,fastening and release of interface plates.

FIG. 9 illustrates a support housing 1400 (hereinafter referred to ashousing 1400) for holding a flexible bioprocess bag according to yetanother embodiment. The housing 1400 may have a similar structure andconfiguration as the housing 1300 and accordingly include similar partsthat perform the same function. The parts that are similar in housing1400 and 1300 may not be described again in detail with respect to FIG.9 . The housing 1400 may have an interface retainer 1402 with aprojecting structure 1404. The projecting structure 1404 may have a slotfor receiving the interface plate of a flexible bioprocess bag. Theflexible bioprocess bag can be placed on a first segment 1406 operablyconnected to a second segment 1408. The interface plate can be slid intothe slot of the projecting structure 1404 in an angular direction whileconnecting both end portions of the flexible bioprocess bag. After theinterface plate is placed in the slot, the projecting structure 1404 canbe collapsed to align to an inner surface 1410 of the first segment1406. Now while unloading the flexible bioprocess bag, the projectingstructure 1404 can be drawn-out from the collapsed state for sliding theinterface plate out from the slot as illustrated in the zoomed view. Themovable retainer 1412 and the projecting structure 1404 assist theoperator 118 to conveniently remove the flexible bioprocess bag from thefirst segment 1406. In another embodiment, the projecting structure 1404can be moved to different heights in vertical direction (shown by arrow1414) so that the interface plate can slid into the slot at varyingangles. This facility provides additional assistance for the operator toload the flexible bioprocess bag 902.

Now moving on to FIG. 10 illustrating a support housing 1500(hereinafter referred to as housing 1500) for holding a flexiblebioprocess bag according to still yet another embodiment. The housing1500 includes a first segment 1502 operatively connected to a secondsegment 1504. The first segment 1502 tiltably opens to access theinterior of the housing 1500 even though not illustrated in FIG. 10 .The first segment 1502 may include an interface retainer 1506 and aretainer 1508. The function of the opening and retainer is explained indetail in conjunction with FIGS. 1 a-i and 6, hence not described here.The first segment 1502 includes two trenches for example, a trench 1510and a trench 1512. After loading the flexible bioprocess bag in thehousing 1500 and connecting tubes to the flexible bioprocess bag, thetubes can be arranged in the trenches 1510 and 1512 by the operator 118.The trenches 1510 and 1512 form part of a tube management structure thatavoids entangling of tubes. In an embodiment, the trenches 1510 and 1512may have additional members that securely fit the tubes in them. Inanother embodiment, there may be clipping or snapping members providedfor securely positioning the tubes in place within the trenches. Thetube management structure (i.e. the trenches 1510 and 1512) illustratedhere is according to one of an exemplary embodiment, and hence it may beenvisioned that the tube management structure may have any otherstructural arrangement for holding the tubes in an organized orconcealed manner. Equally, the trenches may be larger in size and depthand may also protrude from the external surface of the first segment1502 to accommodate the required number and size of tubing. The trenchesmay also be employed for routing cables, for example cables connectingto sensors (like a pressure sensor measuring the head pressure in thegas at the top of the bag) or cables connecting to remote controlledcomponents such as for example valves.

FIG. 11 illustrates a support housing 1600 (hereinafter referred to ashousing 1600) for holding a flexible bioprocess bag according to yetanother exemplary embodiment. The housing 1600 includes a first segment1602 operatively connected to a second segment 1604. The first segment1602 opens and closes in a transverse direction. A supporting part 1606includes one or more openings such as, a mating retainer 1608-1, amating retainer 1608-2 and a mating retainer 1608-3 for holding driveunits. The openings may be aligned in line as illustrated in FIG. 11 .Even though three drive units are held in the corresponding matingretainers, the housing 1600 may have one or more drive units. A flexiblebioprocess bag 1700 as schematically illustrated in FIG. 12 is loaded inthe housing 1600. A flexible bioprocess bag 1700 includes a mixing unit1702-1, a mixing unit 1702-2 and a mixing unit 1702-3 arranged along itsside portion as illustrated in FIG. 12 according to an embodiment. Whenthe supporting part 1606 is positioned in a table configuration, theflexible bioprocess bag 1700 is placed on the supporting part 1606 suchthat the mixing units 1702-1, 1702-2 and 1702-3 are operativelyconnected to corresponding drive units arranged in the mating retainers1608-1, 1608-2 and 1608-3. For sake of convenience of illustration, thedrive units are not illustrated in FIG. 12 . The supporting part 1606 ismoved to a vertical orientation so that the flexible bioprocess bag 1700is positioned in a vertical orientation within the housing 1600. Asdescribed earlier, this is an operating position of the housing 1600 andthe flexible bioprocess bag 1700. In this embodiment, the mixing unitsare present only at the side portion of the flexible bioprocess bag1700, however in other exemplary embodiments, the mixing units may bepresent in the supporting part 1606 and another mixing unit 1704 may bearranged in a bottom portion 1706 of the flexible bioprocess bag 1700which is illustrated in FIG. 12 . The mixing unit 1704 is operativelyconnected to a drive unit through a mating retainer 1610 in a basesegment 1612 of the housing 1600. The first segment 1602 and thesupporting part 1606 may have an opening 1614 and an interface retainer1616. The function of the opening and the interface retainer aredescribed with respect to the earlier figures and hence not described indetail here.

FIG. 13 illustrates a support housing 1800 (hereinafter referred to ashousing 1800) for holding another flexible bioprocess bag 1802 accordingto an exemplary embodiment. The housing 1800 includes a first segment1804 (i.e. a supporting part) operably connected to a second segment1806. A base segment 1808 which is a portion of a base wall 1810 of thehousing 1800 also moves to the vertical orientation when the firstsegment 1804 is arranged in a horizontal orientation parallel to thehorizontal plane or the ground. The base segment 1808 and the firstsegment 1804 may move together or separately to respective orientation.The flexible bioprocess bag 1802 can be placed on the first segment 1804in the table configuration. The flexible bioprocess bag 1802 includes amixing unit 1810 having a shaft 1812 holding a mixing blade 1814-1 and amixing blade 1814-2. The shaft 1812 may be connected to a first endportion 1816 and a second end portion 1818 of the flexible bioprocessbag 1802. In another embodiment, the shaft 1812 may be only connected tothe second end portion 1818. When the flexible bioprocess bag 1802 ispositioned on the first segment 1804, the end of the shaft 1812connected to the first end portion 1816 engages with a drive unitpresent in the base segment 1808.

In an embodiment, the shaft 1812 may be driven by a drive unit arrangedin second end portion 1818 of the flexible bioprocess bag 1802. Thedrive unit may be arranged in the flexible bioprocess bag 1802.Alternatively, the drive unit may be positioned at an end portion 1820of the first segment 1804. When the second end portion 1818 is connectedto a retainer 1822, the shaft 1812 is coupled to the drive unit. The endof shaft 1812 may be automatically or manually coupled to the driveunit. In yet another embodiment, the drive unit may be mounted on thesecond segment 1806 which is fixed. When the first segment 1804 is movedto close the housing 1800 after bag loading, the end of the shaft 1812automatically couples with the drive unit.

In an embodiment, the flexible bioprocess bag 1802 may include twoshafts and a shaft may be connected to the mixing blade 1814-1 andanother shaft to the mixing blade 1814-2. In this case the shafts may bedriven by two separate drive units for running the mixing blades suchas, the mixing blades 1814-1 and 1814-2. In some embodiments, shaftsand/or impellers may be collapsible or foldable to allow a compact sizeduring transport and storage of the bag and may be brought into therespective shape and size for operation during the bag installationprocedure, bag inflation, bag filling or processing.

In an embodiment, the supporting part for loading the flexiblebioprocess bag may not be tilted to form a table configuration—insteadit may tilted only till a certain angle with respect to a horizontalplane as shown in FIG. 14 . FIG. 14 illustrates a support housing 1900(hereinafter referred to as housing 1900) having a first segment 1902(i.e. the supporting part) that is operably connected to a secondsegment 1904. The first segment 1902 is tilted to a certain angle toopen the housing 1900. The flexible bioprocess bag 902 can be loaded onthe first segment 1902 by connecting the first end portion 906 to a basesegment 1906 and connecting the second end portion 908 to a retainer1908. Here, the first segment 1902 may have a wider profile for holdingthe flexible bioprocess bag 902. The retainer 1908 may be similar to theretainer 1308 described with respect to FIG. 8 a even though notillustrated in FIG. 14 . Therefore, the retainer 1908 can move on atrack configured in an inner portion of the first segment 1902. Whileconnecting the second end portion 908, retainer 1908 may move closer tothe base segment 1906. Then, after connecting the second end portion 908to the retainer 1908, the retainer 1908 can move to the top end portionof the first segment 1902. The retainer 1908 stretches-out the flexiblebioprocess bag 902 while moving. The movement of the retainer 1908 canbe controlled manually by the operator 118 or may be controlled by acontrol unit such as the control unit 138. In another embodiment, thefirst segment 1902 may not have the retainer 1908 but can be anyreceiver that can connect to the second end portion 908 of the flexiblebioprocess bag 902 and move along the first segment 1902 to stretch theflexible bioprocess bag 902.

FIG. 15 illustrates a support housing 1910 having a first segment 1912(i.e. the supporting part) that is operably connected to the secondsegment 1904 according to an embodiment. A base segment 1914 isconnected to the first segment 1912. In an embodiment, the base segment1914 is operably connected to the first segment 1912. In someembodiments, the base segment 1914 and the first segment 1912 may bepart of a single unit and hence they together form the supporting part.The first segment 1912 is rotated at an angle with respect to an axis‘A’. For instance, the first segment 1912 may be rotated at 90° angle toopen the housing 1910. Thereafter, the first segment 1912 may be tiltedat an angle as shown in FIG. 15 reducing the footprint of the housing1910. The first segment 1912 may be connected to the second segment 1904using a rotatable connector or any other connection means that enablesthe first segment 1912 to rotatably tilt with respect to the secondsegment 1904. The rotatable connector or the connection means may belocated closer to the base segment 1914. Further, there may be lockingmeans in the rotatable connector or any connection means which enablesthe first segment 1912 to be locked at desired tile angle.

The flexible bioprocess bag can be loaded on the first segment 1912. Itmay be envisioned that the first segment 1912 may be rotated atdifferent angles other than 90° angle and also tilted at differentangles according to various other embodiments. In an embodiment, thefirst segment 1912 can be oriented parallel to the horizontal plane toform the table configuration even though not illustrated in FIG. 15 . Aninterface retainer 1916 in the first segment 1912 and a mating retainer1918 in the base segment 1914 facilitate in holding or retaining theflexible bioprocess bag on the first segment 1912. This is explainedearlier in detail with respect to earlier figures.

FIG. 16 illustrates a flow diagram of a method 2000 of providing aflexible bioprocess bag in a bioreactor according to an embodiment. Thebioreactor includes a support housing (hereinafter referred to ashousing) having a sidewall that includes a first segment and a secondsegment. The first segment is movable in relation to the second segmentbetween an open and closed position. The method 2000 includes loadingthe flexible bioprocess bag on a supporting part arranged in a bagloading position or in a table configuration at step 2002. Thesupporting part is translated from an operating position to the bagloading position. The supporting part is aligned parallel to thehorizontal plane so that the operator or user can conveniently place theflexible bioprocess bag on the supporting part at the ground level. Theflexible bioprocess bag is secured on the flexible bioprocess bag usingone or more retainers at step 2004. In an embodiment the housingincludes a retainer for securing the flexible bioprocess bag on thesupporting part. Once the flexible bioprocess bag is securely loaded,the supporting part is re-translated to an operating position therebypositioning the flexible bioprocess bag within the housing at step 2006.

Turning now to FIG. 17 illustrating a flow diagram of a method 2100 forcultivating cells in a bioreactor. The bioreactor includes a supporthousing (hereinafter referred to as housing) that can hold and mixfluids and contents for cultivating cells. A supporting part of thehousing is translated from the operating position to a bag loadingposition. The supporting part can be aligned with the horizontal planeso that it is configured as the bag loading support surface. Theflexible bioprocess bag is then loaded on the supporting part at step2102. The flexible bioprocess bag is secured on the supporting partusing one or more retainers at step 2104. For loading the flexiblebioprocess bag, a portion of the base i.e., base segment is movedtowards a vertical plane. A bottom portion of the flexible bioprocessbag is connected to the base segment. The flexible bioprocess bagincludes a mixing unit arranged at the bottom portion which can connectto a drive unit configured at the base segment. The drive unit iscapable of driving the mixing unit.

Once loaded, the supporting part is re-translated to the operatingposition thereby positioning the flexible bioprocess bag within thehousing at step 2106. The base segment and the retainers help inorienting the flexible bioprocess bag in the vertical orientation. Thebag interface plate connected to an opening in the supporting part helpsin the radial orientation of the flexible bioprocess bag along at leastone side wall in the housing when in vertical orientation. Once loadedand brought into the vertical orientation, the flexible bioprocess bagcan be inflated and filled with liquid at step 2108. Inflation of theflexible bioprocess bag with air and the filling with liquid forprocessing are typically executed as two subsequent steps. For the stepof filling the flexible bioprocess bag with liquid, the housing will beclosed. In one embodiment, partial inflation or filling of the flexiblebioprocess bag with air and/or liquid can be performed while the housingand the supporting part are not completely closed. The partial inflationand/or filling can help in a stepwise inflation of the flexiblebioprocess bag in the scope of assuming the final shape for operation atoperating liquid volume.

During inflation, the flexible bioprocess bag may inflate in asubstantially radial direction and manner given that retainers at topportion (e.g. a first end portion) and bottom portion (e.g. a second endportion) of the flexible bioprocess bag secure the flexible bioprocessbag in a stretched out alignment along the central axis of the flexiblebioprocess bag arranged in the operating position or verticalorientation.

In order to assist a controlled inflation of the flexible bioprocess bagand thereby achieving a correct sequence and progress in the inflationprocess as well as the flexible bioprocess bag assuming its correctfinal shape, the bag and its film sheets may be fitted in one embodimentwith retainers such as, Velcro tape, snap fit members, securing beltsand so on that are released in a stepwise manner during inflation. Inanother embodiment, the flexible bioprocess bag and film may berestricted during deflation after processing by securing belts orsimilar that help the deflating flexible bioprocess bag to assume ashape that allows the tilting of supporting part with the deflatedflexible bioprocess bag such that the integrity of the flexiblebioprocess bag is not compromised and/or the flexible bioprocess bag iswithin the inner surface of the supporting part.

The flexible bioprocess bag is connected to multiple feed tubes that arecapable of feeding culture medium and cells into the flexible bioprocessbag at step 2108. In addition to culture medium and cells, othercontents such as, buffer, base, oxygen and other gases may be also fedinto the flexible bioprocess bag at step 2110. The mixing unit is usedto mix the contents filled in the flexible bioprocess bag. The mixingprocess enables contents to be mixed properly so that the cells can becultivated properly at step 2112. It is critical to control the mixingunit mixing speed and other parameters which determines how effectivelythe oxygen can be supplied to cells and avoid any cell damage.

FIG. 18 illustrates a flexible bioprocess bag 2200 according to anembodiment. The flexible bioprocess bag 2200 includes one or more wallssuch as, a wall 2202 that form an interior of the flexible bioprocessbag 2200. In an embodiment, an inner wall defines the interior of theflexible bioprocess bag 2200. The flexible bioprocess bag 2200 includesone or more fluid ports at an end portion 2204 (i.e. first end portion)of the wall 2202. The one or more fluid ports for example, fluid ports2206-1, 2206-2, 2206-3, 2206-4 and 2206-5, may be held by a firstinterface plate 2208. The first interface plate 2208 may be held in aholding means 2209. In an embodiment, the first interface plate 2208 mayhave the fluid ports 2206-1, 2206-2, 2206-3, 2206-4 and 2206-5 as itsintegral part. In another embodiment, the first interface plate 2208 maybe modular and accordingly it can arrange or add or reduce fluid portsbased on the requirement of the operator. Moreover, the fluid ports canalso be arranged in the first interface plate 2208 in a differentmanner. For instance, all fluid ports may be arranged in a line.Alternatively, the fluid ports may be arranged in a differentconfiguration in the first interface plate 2208.

The flexible bioprocess bag 2200 may include one or more sensor portssuch as, sensor ports 2210-1, 2210-2, 2210-3, 2210-4 and 2210-5 held ina second interface plate 2212. The second interface plate 2212 may bepositioned at a portion substantially proximal to the end portion 2204of the flexible bioprocess bag 2200. The second interface plate 2212 isheld by a holding means 2213. In an embodiment, the second interfaceplate 2212 may have the sensor ports 2210-1, 2210-2, 2210-3, 2210-4 and2210-5 as its integral part. In another embodiment, the second interfaceplate 2212 may be modular and accordingly it can arrange or add orreduce sensor ports based on the requirement of the operator. Moreover,the sensor ports can also be arranged in the second interface plate 2212in a different manner. For instance, all sensor ports may be arranged ina line. Alternatively, the sensor ports may be arranged in a differentconfiguration in the second interface plate 2212.

In an alternate embodiment, the flexible bioprocess bag 2200 may haveonly one of the first interface plate 2208 and the second interfaceplate 2212 holding respective fluid ports and sensor ports.

The flexible bioprocess bag 2200 may have an exhaust outlet 2214 at anend portion 2216 (i.e. second end portion). An exhaust tube 2218 isconnected to the exhaust outlet 2214 by the operator. A connector 2220connects the exhaust tube 2218 to the exhaust outlet 2214. Duringoperation, various exhaust gases are expelled through the exhaust outlet2214 and then passes out through the exhaust tube 2218. The exhaustgases may need to be filtered when passed out to the atmosphere. Theoperator may connect one or more filters such as, a filter 2222-1 and afilter 2222-2 to the exhaust outlet 2214 through the exhaust tube 2218.The filter 2222-1 and the filter 2222-2 may be same type of filters ordifferent types of filters. In another embodiment, even though only twofilters are shown to be present, however there can be other exhaustfilters that act as back-up exhaust filters which can function when thefilters 2222-1 and 2222-2 are blocked. These filters are positioned suchthat it is easily accessible for the operator standing on the floor. Thefilter 2222-2 can be connected to the tube 2226 through a connector2227. This provides an advantage of performing ground level operation bythe operator. Condensation can occur within the tube 2218, and thereforea pump 2224 may be used to pump back the condensate into the flexiblebioprocess bag 2200 through a tube 2226. The tube 2226 is connected tothe flexible bioprocess bag 2200 through a connector 2228. Further whileperforming operation in the flexible bioprocess bag 2200, there may be aneed for gas (e.g. overlay gas) to be supplied to the ingredients orcontents of the flexible bioprocess bag 2200. This overlay gas may needto supplied through a gas port 2229 arranged at the end portion 2216 ofthe wall 2202. A gas tube 2230 is connected to the gas port 2229 througha connector 2232.

Connectors for connecting components or tubing in fluid contact with themixing unit, which are connected external and adjacent to the flexiblebioprocess bag 2200, like the shown exemplary connectors 2220 and 2227,may be provided in different configurations. The components external andadjacent to the flexible bioprocess bag 2200 typically comprise liquidaddition or removal lines, gas addition and exhaust gas removal lines,sensors, mixing elements, sparging elements etc. and may come withdifferent sizes, shapes and diameters in the connection to the flexiblebioprocess bag. One configuration for a connection is of fixed type, forexample tubing port welded into the wall of the flexible bioprocess bag2200, the tubing port providing a barb connection for attaching thetubing. Similar fixed connections may be provided for attaching sensorsetc., to the flexible bioprocess bag. Components attached to theflexible bioprocess bag using fixed type connections are typicallypre-sterilized together with the flexible bioprocess bag. Another typeof connection provides an aseptic connection feature, hereby allowingtwo separate pre-sterilized components to be connected at the point ofuse while maintaining the sterility in the internal volume of thesecomponents. Aseptic connectors that allow for a connection in differentsizes are provided by GE Healthcare™ (e.g., ReadyMate™ Connectors), forexample. The use of aseptic connections allows for handling andinstalling components of the mixing unit and bioreactor in subsequentsteps, hereby reducing the size, complexity and weight of componentsduring the installation steps and thereby enhancing ergonomics and easeof use. The modularity provided by the use of aseptic connectorsincreases also the flexibility in combining different components withdifferent properties depending on the specific application needs.Further, the modularity allows for increased flexibility in packaging,storage and transport of the components. Aseptic connections may beapplied adjacent to the walls of the flexible bioprocess bag or intubing sections along the length of tubing. In another embodiment, themixing unit and flexible bioprocess bag are provided with asepticdisconnectors that allow for a disassembly of the mixing unit duringprocessing and in particular after processing when removing the flexiblebioprocess bag from the vessel. Aseptic disconnectors facilitate aclosed system approach during assembly and can protect the operator andenvironment from exposure to fluids internal to the mixing unit andflexible bioprocess bag.

The flexible bioprocess bag 2200 may have a gas sparging unit 2234 (alsocalled a sparger) arranged at a bottom portion (i.e. at the end portion2204) of the wall 2202. The gas sparging unit 2234 supplies gas into theflexible bioprocess bag 2200. The gas is utilized by the ingredients orcontents in the flexible bioprocess bag 2200. The function of the gassparging unit 2234 is explained earlier.

The flexible bioprocess bag 2200 includes a drain port 2236 for drainingthe contents from the flexible bioprocess bag 2200. The contents may beingredients or any matter that are unwanted. Drain port 2236 ispreferably allowing full drainability of the flexible bioprocess bag andreactor volume and the opening of the drain port 2236 at the internal ofthe flexible bioprocess bag are therefore positioned at a lowest pointin the flexible bioprocess bag 2200. For example, during a bioprocessoperation or mixing process there may be ingredients that are formed andmay be unwanted which needs to be drained through the drain port 2236.Alternatively, the contents from the flexible bioprocess bag 2200 may bedrained out using the drain port 2236 for emptying and subsequentoptional rinsing or flushing of the flexible bioprocess bag 2200. In analternate embodiment, the tube 2226 can be connected to one of the drainport 2236 and the gas sparging unit 2234.

The flexible bioprocess bag 2200 may be loaded in a housing similar toany of the housings described in FIGS. 1 a-h and FIG. 2 . After theflexible bioprocess bag 2200 is inflated the tubes 2230, 2218 and 2226can be connected to respective connectors 2232, 2220, 2228 and 2227provided in the flexible bioprocess bag 2200. Alternatively, theflexible bioprocess bag 2200 may be a standalone unit for holdingsolutions or fluids or ingredients or contents.

In some embodiments of the support housing 2400 for the bioprocess bag2402 disclosed above, illustrated in FIG. 22 , the first segment 2404comprises a first drive unit 2410 for connecting and driving a firstmixing unit 2415 in the flexible bioprocess bag. This drive unit cansuitably be a magnetic drive unit. Further, the base segment 2420 or theside wall may comprise a second drive unit 2425 (e.g. a magnetic driveunit) for connecting to a second mixing unit 2430 in the flexiblebioprocess bag. The base segment or side wall may also comprise a matinggas supply retainer (not shown in FIG. 22 ) adjacent to the second driveunit for connecting to a sparger 2435 in the flexible bioprocess bag,adjacent to the second mixing unit. In FIG. 22 , the first segment 2404and the base segment 2420 are shown as being tiltable around ahorizontal axis 2440.

In some embodiments of the above method of providing a flexiblebioprocess bag 2402 in a bioreactor, the first segment 2404 may likewisecomprise a first drive unit 2410 for connecting and driving a firstmixing unit 2415 in the flexible bioprocess bag. This drive unit cansuitably be a magnetic drive unit. Further, the base segment 2420 or theside wall may comprise a second drive unit 2425 (e.g. a magnetic driveunit) for connecting to a second mixing unit 2430 in the flexiblebioprocess bag. The base segment or side wall may also comprise a matinggas supply retainer (not shown) adjacent to the second drive unit forconnecting to a sparger 2435 in the flexible bioprocess bag, adjacent tothe second mixing unit.

In certain embodiments of the flexible bioprocess bag 2402; 2502 asdisclosed above, illustrated in FIGS. 21 and 22 , a side wall 2445; 2508of the flexible bioprocess bag comprises a first mixing unit 2415; 2515configurated to be connected to a first drive unit 2410; 2510 in saidsupporting part 2404. The bag may further comprise a sparging unit 2435;2535 attachable to a mating gas supply retainer (not shown) provided ata portion of the support housing. It may also comprise a second mixingunit 2430; 2530 configurated to be connected to a second drive unit2425; 2525 of the support housing. Suitably, the sparging unit and thesecond mixing unit can be provided adjacent to each other in theflexible bioprocess bag, e.g. as illustrated in FIG. 23 .

In a further aspect, the invention discloses a flexible bioprocess bag2402; 2502 comprising a first mixing unit 2415; 2515 configured foragitating a content of the flexible bioprocess bag and a second mixingunit 2430; 2530, adjacent to a sparging unit 2435; 2535, and configuredfor controlling the size and distribution of bubbles emanating from thesparging unit. One or both of the first and second mixing units cansuitably be magnetically driven. The first mixing unit may e.g. beprovided on a side wall 2408; 2508 of the flexible bioprocess bag. Thesecond mixing unit and the sparging unit may e.g. be provided on abottom wall 2406; 2506 of the flexible bioprocess bag. Suitably thefirst mixing unit has an impeller 2417; 2517 which is located away fromthe bottom wall of the flexible bioprocess bag, which is advantageousfor bulk mixing of the fluid in the bag. The impeller may e.g. belocated at a distance 2518 of at least 5%, or at least 10%, of the innerheight 2519 of the flexible bioprocess bag from the bottom wall 2506.This can apply both for side wall- and bottom-wall mounted mixing units.If the first mixing unit is bottom-mounted (not shown), the impellerthen needs to be mounted on a shaft to provide the distance from thebottom. The impeller 2417; 2517 of the first mixing unit can suitably bean axial flow impeller, e.g. a segmented or pitched blade impeller. Forthe second mixing unit, good bubble dispersion can be achieved with animpeller 2432; 2532 close to the sparging unit, e.g. where the distancefrom the impeller to the sparging unit is less than 5 cm, such as lessthan 2 cm or 0.5-1 cm. The impeller 2432; 2532 in the second mixing unitmay e.g. be a segmented or pitched blade impeller, as illustrated inFIG. 23 . The impeller diameter can suitably be less than 0.5 times thediameter of the bag, such as less than 0.4 times the bag diameter or0.3-0.4 times the bag diameter. The sparging unit can be shaped as oneor more discs, as in FIG. 23 , but also other shapes are possible—e.g.porous ring structures. By decoupling the bulk mixing from the bubbledispersion, both processes can be better optimized in comparison to thecase where one mixing unit has a double function. The efficiency of abulk mixing unit, in this case a side wall-mounted axial flow impeller,is illustrated by the CFD simulations of FIGS. 19 and 20 . FIG. 19 a )shows a reference bottom-mounted impeller in a flat-bottomed 500 Lcylindrical vessel, with tracer locations P1 to P8 according to FIG. 19c ), giving the mixing time of 60 s (T95— time to 95% mixinghomogeneity). In contrast, the side wall impeller of FIG. 19 b ) and d)gives a mixing time T95 of 38 s. FIG. 20 shows the flow pattern of theside wall-mounted impeller across a central vertical plane of thevessel.

In a yet further aspect, the invention discloses a support housing 2400;2500 for a flexible bioprocess bag 2402; 2502, comprising a first driveunit 2410; 2510 (e.g. a magnetic drive unit) and a second drive unit2425; 2525 (e.g. a magnetic drive unit) for connecting and driving afirst mixing unit 2415; 2515 and a second mixing unit 2430; 2530respectively in a flexible bioprocess bag when mounted in said supporthousing, where the first drive unit may be provided on a side wall 2504or side wall segment 2404 of the support housing. The second drive unitmay e.g. be provided on a bottom wall 2520 or bottom wall segment 2420of said support housing. The support housing may further comprise amating gas supply retainer (not shown) adjacent to the second drive unitfor connecting to a sparging unit 2435; 2535 in the flexible bioprocessbag, adjacent to the second mixing unit. Suitably, the power of thefirst drive unit may be at least 2 times the power of the second driveunit, such as at least 5 times or at least 10 times the power of saidsecond drive unit. More power is needed for bulk agitation than forbubble dispersion and it can be advantageous to design the system suchthat the second mixing unit primarily disperses bubble away from thesparger, while the larger first mixing unit provides bulk mixing,including mixing the dispersed bubbles into the bulk fluid.

In some embodiments, illustrated by FIG. 24 a ) and b), the inventiondiscloses a support housing 2600 for a flexible bioprocess bag 2602,comprising a drive unit 2610 having an acute angle α relative to a basesegment 2620 of said support housing. The drive unit is arranged forconnecting and driving a shaft 2611 with a plurality of mixing units2615, 2616, 2617 in the flexible bioprocess bag. This drive unit cansuitably be a magnetic drive unit and is suitably arranged in basesegment 2620 or in a recess of the base segment. As described above, afirst segment 2603 of a side wall 2604 and the base segment 2620 aretiltable relative to a second segment 2606 of the side wall, suitablyaround a horizontal axis 2640. The base segment may also comprise amating gas supply retainer 2632 adjacent to the drive unit forconnecting to a sparger 2635 in the flexible bioprocess bag. Firstsegment 2603 may further comprise a bearing retainer 2612, arranged toengage or interact with a bearing 2638 or bearing holder 2637 on a sidewall 2639 of the flexible bioprocess bag, such that a shaft 2611 with aplurality of mixing units in a bag 2602 is rotatably supported at adistal end by the bearing and/or bearing holder and at a proximal end bythe drive unit.

The invention further discloses a flexible bioprocess bag 2602,comprising a shaft 2611 with a plurality of mixing units 2615, 2616,2617 configured for agitating a content of the flexible bioprocess bag.The shaft is arranged to be driven by the drive unit 2610 in the supporthousing 2600 and, if the drive unit is a magnetic drive unit, the shaftmay suitably comprise a set of magnets arranged to couple with a set ofpermanent magnets or electromagnets in the drive unit. The shaft cansuitably be aligned with the drive unit along a common axis of rotation2641, having an acute angle α in relation to base segment 2620. α maye.g. be in the range of 50-80 degrees, such as 55-75 degrees. A distalend 2642 of shaft 2611 may be rotatably attached to a side wall 2639 ofthe flexible bioprocess bag, e.g. by a bearing 2638. The bearing 2638may be directly attached to side wall 2639, or it may be attached via abearing holder 2637, which can e.g. be a rigid plastic structure weldedto the side wall of the bag. The bearing holder, or the bearing, mayengage a bearing retainer 2632 on the first segment 2603 of the supporthousing side wall. It is also contemplated that the bearing holder andthe bearing retainer may comprise magnets, allowing magnetic coupling tofix the bearing holder in a correct position. If the side wall of thesupport housing is perpendicular to the base of the housing, the anglebetween the side wall and the shaft will be 90 degrees—α, such that thisangle may e.g. be in the range of 10-40 degrees, such as 15-35 degrees.The mixing units can comprise a first mixing unit 2615, a second mixingunit 2616 and optionally a third mixing unit 2617. The first mixing unit2615 can be located at a proximal end 2618 of the shaft, close to thedrive unit and sparger 2635. The first mixing unit can then be designedfor efficient dispersion of air/gas bubbles from the sparger into thecontent of the bag. For this purpose, the first mixing unit can e.g. bea radial mixing unit such as e.g. a Rushton turbine. The second andoptional third mixing units can be designed for mixing of the bagcontent and can e.g. be angled blade (e.g. propeller) agitators toprovide for axial mixing.

In certain embodiments, illustrated by FIG. 25 a ) and b), the inventiondiscloses a support housing 2700 for a flexible bioprocess bag 2702,comprising a drive unit 2710 having an acute angle α relative to a basesegment 2720 of said support housing. The drive unit is arranged forconnecting and driving a shaft 2711 with a plurality of mixing units2715, 2716, 2717 in the flexible bioprocess bag. This drive unit cansuitably be a magnetic drive unit and is suitably arranged in basesegment 2720 or in a recess of the base segment. The base segment mayalso comprise a mating gas supply retainer 2732 adjacent to the driveunit for connecting to a sparger 2735 in the flexible bioprocess bag. Asdescribed above, a first segment 2703 of a side wall 2704 and the basesegment 2720 are tiltable relative to a second segment 2706 of the sidewall, suitably around a horizontal axis 2740. In addition, a baffle orshaft holder rod 2712 on the side wall opposite first segment 2703 istiltable along with base segment 2720. A bearing retainer 2743 locatedon or integral with baffle or shaft holder rod 2712 is arranged toengage or interact with a bearing 2738 or bearing holder 2737 on a sidewall 2739 of the flexible bioprocess bag, such that a shaft 2711 with aplurality of mixing units in bag 2702 is rotatably supported at a distalend by the bearing and/or bearing holder and at a proximal end by thedrive unit.

The invention further discloses a flexible bioprocess bag 2702,comprising a shaft 2711 with a plurality of mixing units 2715, 2716,2717 configured for agitating a content of the flexible bioprocess bag.The shaft is arranged to be driven by the drive unit 2710 in the supporthousing 2700 and, if the drive unit is a magnetic drive unit, the shaftmay suitably comprise a set of magnets arranged to couple with a set ofpermanent magnets or electromagnets in the drive unit. The shaft cansuitably be aligned with the drive unit along a common axis of rotation2741, having an acute angle α in relation to base segment 2720. α maye.g. be in the range of 50-80 degrees, such as 55-75 degrees. A distalend 2742 of shaft 2711 may be rotatably attached to a side wall 2739 ofthe flexible bioprocess bag, e.g. by a bearing 2738. The bearing 2738may be directly attached to side wall 2739, or it may be attached via abearing holder 2737, which can e.g. be a rigid plastic structure weldedto the side wall of the bag. The bearing holder, or the bearing, mayengage a bearing retainer 2743 located on or integral with a baffle orshaft holder rod 2712, opposite the first segment 2703 of the supporthousing side wall. It is also contemplated that the bearing holder 2737and the baffle/shaft holder rod 2712 may comprise magnets, allowingmagnetic coupling to fix the bearing holder in a correct position. Ifthe side wall of the support housing is perpendicular to the base of thehousing, the angle between the side wall and the shaft will be 90degrees—α, such that this angle may e.g. be in the range of 10-40degrees, such as 15-35 degrees. The mixing units can comprise a firstmixing unit 2715, a second mixing unit 2716 and optionally a thirdmixing unit 2717. The first mixing unit 2715 can be located at aproximal end 2718 of the shaft, close to the drive unit and sparger2735. The first mixing unit can then be designed for efficientdispersion of air/gas bubbles from the sparger into the content of thebag. For this purpose, the first mixing unit can e.g. be a radial mixingunit such as e.g. a Rushton turbine. The second and optional thirdmixing units can be designed for mixing of the bag content and can e.g.be angled blade (e.g. propeller) agitators to provide for axial mixing.

From the foregoing, it will be appreciated that the bioreactor includesa housing that enables a user or operator to load a flexible bioprocessbag in a convenient manner. A supporting part of the housing is movableto be aligned to the horizontal plane attaining a table configuration.Thus, the operator or user can load the flexible bioprocess bag on thesupporting part at ground level conveniently. The flexible bioprocessbag can be securely positioned on the supporting part using retainers bythe operator. Also, the bioprocess can be connected to multiple feedtubes that are for supplying buffer, culture medium, gases, base and soon to the flexible bioprocess bag at the ground level. The supportingpart eliminates the need for the operator to climb up the bioreactor formaking connections of feed tubes to the flexible bioprocess bag. Asloading of the flexible bioprocess bag happens in the ground level thetime required for setting up the bioreactor is reduced, it provides abetter user experience.

This written description uses examples to disclose the invention,including the best mode, and also to enable any person skilled in theart to practice the invention, including making and using any computingsystem or systems and performing any incorporated methods. Thepatentable scope of the invention is defined by the claims, and mayinclude other examples that occur to those skilled in the art. Suchother examples are intended to be within the scope of the claims if theyhave structural elements that do not differ from the literal language ofthe claims, or if they include equivalent structural elements withinsubstantial differences from the literal language of the claims.

We claim:
 1. A support housing, comprising: a housing body having a topsurface, a bottom wall, and a sidewall extending from the bottom wall tothe top surface, an inner region between the top surface, the bottomwall and the sidewall defining an internal volume of the housing body,the sidewall including a first sidewall segment, a second sidewallsegment, and a third sidewall segment disposed about the first sidewallsegment and the second sidewall segment to support a flexible bioprocessbag, the third sidewall segment having a main wall that receives theflexible bioprocess bag thereon, a base wall perpendicular to the mainwall with an opening therein to receive an end portion of the flexiblebioprocess bag, the base wall having a surface area that is less than asurface area of the main wall, and one or more retainers to hold theflexible bioprocess bag in place against the main wall and the endportion of the flexible bioprocess bag in the opening of the base wall,wherein the first sidewall segment is movable in relation to the secondsidewall segment, the first sidewall segment movable between an openposition in that the first sidewall segment moves away from the secondsidewall segment to provide access to the internal volume of the housingbody and a closed position in that the first sidewall segment is alignedwith the second sidewall segment to preclude access to the internalvolume, wherein the third sidewall segment is hingedly connected to thehousing body by a hinged mechanism for tiltable translation of the thirdsidewall segment in relation to the first sidewall segment and thesecond sidewall segment, the third sidewall segment tiltablytranslatable at an angle to a longitudinal axis extending through theinternal volume of the housing body, the angle of translation of thethird sidewall segment extending between a horizontal orientationparallel with a horizontal axis extending away from the bottom wall ofthe housing body and a vertical orientation parallel with thelongitudinal axis, the horizontal orientation defining a loadingposition for the main wall of the third sidewall segment to receive theflexible bioprocess bag thereon with the end portion of the flexiblebioprocess bag in the opening of the base wall of the third sidewallsegment, the vertical orientation defining an operation position tooperate the flexible bioprocess bag after securing the flexiblebioprocess bag to the main wall and the end portion of the flexiblebioprocess bag in the opening of the base wall with the one or moreretainers and tiltingly translating the third sidewall segment from thehorizontal orientation to the vertical orientation, the base wallprotruding outward from the main wall to the inner region of the housingbody when the third sidewall is in the vertical orientation to form apart of the bottom wall.
 2. The support housing of claim 1, wherein thefirst sidewall segment is tiltably movable in relation to the secondsidewall segment.
 3. The support housing of claim 1, wherein the thirdsidewall segment is integral to the first sidewall segment.
 4. Thesupport housing of claim 1, wherein the third sidewall segment istranslatable at an inclination angle less than 45 degrees above or belowa horizontal plane.
 5. The support housing of claim 1, wherein the thirdsidewall segment is translatable to a position less than 150 cm fromground level.
 6. The support housing of claim 1, wherein the firstsidewall segment is collapsible in a longitudinal direction.
 7. Thesupport housing of claim 1, wherein the first sidewall segment iscollapsible in a transverse direction.
 8. The support housing of claim1, wherein the third sidewall segment is collapsible in a longitudinaldirection.
 9. The support housing of claim 1, wherein the third sidewallsegment is collapsible in a transverse direction.
 10. The supporthousing of claim 1, wherein a portion of the base wall of the thirdsidewall segment is movable towards a vertical plane.
 11. The supporthousing of claim 10, wherein the portion of the base wall is movabletowards a horizontal plane upon re-translation of the third sidewallsegment to the operation operating position.
 12. The support housing ofclaim 1, wherein the flexible bioprocess bag comprises a mixing unit.13. The support housing of claim 12, wherein the base wall comprises amagnetic drive unit for connecting to the mixing unit in the flexiblebioprocess bag.
 14. The support housing of claim 1, wherein the basewall or one of the first sidewall segment and the second sidewallsegment comprises a mating gas supply retainer adjacent to a seconddrive unit for connecting to a sparger in the flexible bioprocess bag,adjacent to a second mixing unit.
 15. The support housing of claim 1,further comprising a tube management structure for organizing a tube anda connector connected to the flexible bioprocess bag.
 16. The supporthousing of claim 1, wherein the one or more retainers comprises at leastone interface retainer provided in the third sidewall segment, whereinthe at least one interface retainer is positioned on the third sidewallsegment and attachable to an interface plate of the flexible bioprocessbag.
 17. The support housing of claim 16, wherein the interface retaineris variable in at least one direction.
 18. The support housing of claim1, further comprising at least one sensor provided in at least one ofthe third sidewall segment, the first sidewall segment and the secondsidewall segment, wherein a sensor of the at least one sensor determinesa position of the third sidewall segment and an object adjacent to thesupport housing.
 19. The support housing of claim 1, wherein the one ormore retainers comprises a retainer attachable to a mating retainingmember of the flexible bioprocess bag.
 20. A support housing for aflexible bioprocess bag, the support housing comprising avertically-oriented cylindrical housing body having a top surface, abottom wall, and a curved sidewall extending from the bottom wall to thetop surface, an inner region between the top surface, the bottom walland the curved sidewall defining an internal volume of the housing body,the curved sidewall including a first sidewall segment, a secondsidewall segment, and a third sidewall segment disposed about the firstsidewall segment and the second sidewall segment to support the flexiblebioprocess bag, the third sidewall segment having a main wall thatreceives the flexible bioprocess bag thereon, a base wall perpendicularto the main wall with an opening therein to receive an end portion ofthe flexible bioprocess bag, the base wall having a surface area that isless than a surface area of the main wall, and one or more retainers tohold the flexible bioprocess bag in place against the main wall and theend portion of the flexible bioprocess bag in the opening of the basewall, wherein the first sidewall segment is movable in relation to thesecond sidewall segment, the first sidewall segment movable between anopen position in that the first sidewall segment moves away from thesecond sidewall segment to provide access to the internal volume of thehousing body and a closed position in that the first sidewall segment isaligned with the second sidewall segment to preclude access to theinternal volume, wherein the third sidewall segment is hingedlyconnected to the housing body by a hinged mechanism for tiltabletranslation of the third sidewall segment in relation to the firstsidewall segment and the second sidewall segment, the third sidewallsegment tiltably translatable at an angle to a longitudinal axisextending through the internal volume of the housing body, the angle oftranslation of the third sidewall segment extending between a horizontalorientation parallel with a horizontal axis extending away from thebottom wall of the housing body and a vertical orientation parallel withthe longitudinal axis, the horizontal orientation defining a loadingposition for the main wall of the third sidewall segment to receive theflexible bioprocess bag thereon with the end portion of the flexiblebioprocess bag in the opening of the base wall of the third sidewallsegment, the vertical orientation defining an operation position tooperate the flexible bioprocess bag after securing the flexiblebioprocess bag to the main wall and the end portion of the flexiblebioprocess bag in the opening of the base wall with the one or moreretainers and tiltingly translating the third sidewall segment from thehorizontal orientation to the vertical orientation, the base wallprotruding outward from the main wall to the inner region of the housingbody when the third sidewall is in the vertical orientation to form apart of the bottom wall.
 21. The support housing of claim 20, whereinthe first sidewall segment is operably connected to the second sidewallsegment.
 22. The support housing of claim 20, wherein the third sidewallsegment is integral to the first sidewall segment.
 23. The supporthousing of claim 20, wherein the base wall is movable towards a verticalplane.
 24. The support housing of claim 23, wherein the base wall ismovable towards the vertical plane along with a tiltable translation ofthe third sidewall segment.
 25. The support housing of claim 23, whereinthe base wall is movable towards a horizontal plane upon re-translationof the third sidewall segment to the operation position and movement ofthe first sidewall segment to the closed position.
 26. The supporthousing of claim 23, wherein the flexible bioprocess bag comprises atleast one port at a first end portion and a liquid feed port at a secondend portion, wherein upon re-translation of the third sidewall segmentto the operation position the first end portion of the flexiblebioprocess bag is at a top end of the support housing and the second endportion is at the bottom wall of the support housing.